Isoxazole(isothiazole)-5-carboxamides

ABSTRACT

Isoxazole(isothiazole)-5-carboxamides of the formula ##STR1## where X is oxygen or sulfur, 
     R 1  is hydrogen, substituted or unsubstituted alkyl, alkoxy, substituted or unsubstituted cycloalkyl, a 5- or 6-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, and which may be substituted, or substituted or unsubstituted phenyl, or 
     R 2  is formyl, 4,5-dihydrooxazol-2-yl or a radical of the formula COYR 5  or CONR 6  R 7 , where 
     Y is oxygen or sulfur, 
     R 5  is 
     hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, haloalkenyl, substituted or unsubstituted alkynyl, 
     cycloalkyl, 
     cycloalkenyl, 
     substituted or unsubstituted phenyl, 
     a 5- or 6-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, 
     cycloalkanimino, phthalimido, succinimido, or a radical ##STR2## R 3  and R 4  have the meanings defined herein, or their agriculturally acceptable salts possess herbicidal activity.

The present invention relates to substituted isoxazole- and isothiazole-5-carboxamides and their use for controlling undesirable plant growth.

Isoxazole- and isothiazolecarboxylic acids and their derivatives are known. These are 5-aminocarbonyl-3-methylisoxazole-4-carboxylic acid, ethyl 5-aminocarbonyl-3-methylisoxazole-4-carboxylate, isothiazole-4,5-dicarboxamide and 5-carbamoylisothiazole-4-carboxylic acid (J. Chem. Soc. Perkin Trans. I 1982, 2391; J. Heterocycl. Chem. 22 (1985), 1561 and J. Chem. Soc. 1959, 3061). Possible uses of these substances are not described.

We have found that isoxazole(isothiazole)-5-carboxamides of the formula Ia ##STR3## where X is oxygen or sulfur,

R¹ is hydrogen,

C₁ -C₁₀ -alkyl which is unsubstituted or substituted by C₁ -C₃ -alkoxy, C₁ -C₃ -haloalkoxy, halogen, cyano or phenyl which may be substituted by halogen, C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alklthio, C₁ -C₄ -haloalkylthio, cyano or nitro, C₁ -C₄ -alkoxy,

C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₄ -alkyl or halogen,

a 5-membered or 6-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, which may be substituted by C₁ -C₄ -alkyl, carboxyl or C₁ -C₄ -alkoxycarbonyl,

or phenyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₈ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro or cyano,

R² is formyl, 4,5-dihydrooxazol-2-yl or a radical of the formula COYR⁵ or CONR⁶ R⁷, where

Y is oxygen or sulfur,

R⁵ is hydrogen,

C₁ -C₈ -alkyl which may be substituted by C₁ -C₄ -alkoxy, C₁ -C₄ -alkoxy-C₁ -C₄ -alkoxy, halogen, cyano, hydroxyl, trimethylsilyl, C₁ -C₄ -alkylthio, C₁ -C₄ -alkylamino, C₁ -C₄ -dialkylamino, C₁ -C₄ -alkylsulfinyl, C₁ -C₄ -alkylsulfonyl, carboxyl, C₁ -C₄ -alkoxycarbonyl, C₁ -C₄ -dialkylaminocarbonyl, C₁ -C₄ -dialkoxyphosphonyl, alkyliminooxy, benzyloxy, benzoyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₃ -alkoxy or halogen, or phenyl which is unsubstituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano, or may be substituted by thienyl, furyl, tetrahydrofuryl, phthalimido or pyridyl,

C₃ -C₈ -alkenyl which is unsubstituted or substituted by phenyl which may be substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano, C₃ -C₅ -haloalkenyl,

C₃ -C₈ -alkynyl which is unsubstituted or substituted by hydroxyl or C₁ -C₄ -alkoxy,

C₃ -C₆ -cycloalkyl,

C₅ - or C₆ -cycloalkenyl,

phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro, cyano, C₁ -C₄ -alkoxycarbonyl or acylamino,

a 5-membered or 6-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen or a benzotriazole radical,

C₆ - or C₇ -cycloalkylimino, phthalimido, succinimido, or a radical ##STR4## or one equivalent of a cation from the group consisting of the alkali metals, alkaline earth metals, manganese, copper, iron, ammonium and substituted ammonium, or a radical ##STR5## where R⁸ and R⁹ independently of one another are each C₁ -C₄ -alkyl, C₂ -C₅ -alkoxyalkyl, C₃ -C₈ -cycloalkyl, phenyl or furyl or together form a methylene chain of the formula --(CH₂)_(m) --, where m is from 4 to 7, and R⁹ is additionally hydrogen,

R⁶ is hydrogen, C₁ -C₈ -alkyl or C₃ -C₈ -cycloalkyl and

R⁷ is hydrogen or C₁ -C₈ -alkyl, or

R⁶ and R⁷ form a methylene chain having 4 or 5 members,

R³ is hydrogen,

C₁ -C₈ -alkyl which is unsubstituted or substituted by hydroxyl, halogen, C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio or C₁ -C₄ -dialkylamino

or C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, halogen or C₁ -C₄ -haloalkyl, and

R⁴ is hydrogen, hydroxyl, C₁ -C₄ -alkoxy,

C₁ -C₁₀ -alkyl which is unsubstituted or substituted by C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -dialkylamino, halogen, C₃ -C₆ -cycloalkyl or phenyl which may be substituted by halogen, cyano, nitro, C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio or C₁ -C₄ -halo-alkylthio,

C₃ -C₁₀ -alkynyl or

C₃ -C₁₀ -alkenyl which is unsubstituted or substituted by halogen or C₁ -C₄ -alkoxy,

C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by

C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro or cyano,

C₁ -C₄ -dialkylamino, a 3-membered to 6-membered heterocyclic radical which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl or halogen and has one or two heteroatoms selected from the group consisting of oxygen, sulfur and unsubstituted or methylsubstituted nitrogen, naphthyl, or phenyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitrogen, cyano, formyl, C₁ -C₆ -alkanoyl or C₁ -C₆ -haloalkanoyl,

or R³ and R⁴ together form a radical of the structure --(CH₂)_(n) --Y_(p) --(CH₂)_(q) --, where n and q are each 1, 2 or 3, p is 0 or 1 and Y is oxygen, sulfur or N-methyl, or the radical of the formula

    --(CH.sub.2).sub.2 --CO--

and their agriculturally acceptable salts possess herbicidal activity.

The methyl, alkoxy, alkenyl and alkynyl radicals R¹, R³, R⁴, R⁵, R⁶ and R⁷ may be straight-chain or branched and are preferably of 1 to 4 carbon atoms. The same applies to the alkyl radicals which may be present as substituents in the radicals R¹, R³, R⁴, R⁵, R⁶ and R⁷, and to the alkyl groups in the haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, dialkylamino, alkanoyl, haloalkanoyl and alkoxycarbonyl radicals.

Preferred halogen substituents are chlorine substituents.

The heterocyclic radicals R¹ are saturated or unsaturated. Suitable examples are tetrahydropyranyl, tetrahydrofuryl, pyrazolyl, thienyl, furyl, pyridyl and tetrahydrofuryl. These radicals may be substituted by C₁ -C₄ -alkyl, carboxyl or C₁ -C₄ -alkylcarbonyl.

The heterocyclic radicals R⁵ may be saturated or unsaturated. Suitable radicals are thienyl, furyl, tetrahydrofuryl, triazolyl, imidazolyl, tetrahydropyranyl, pyridyl, morpholino and piperidino.

Saturated or unsaturated heterocyclic radicals R⁴ are, for example, tetrahydropyranyl, tetrahydrofuryl, thiazolyl, pyridyl, morpholino, piperidino and pyrimidyl.

The novel compounds I can form addition salts, for example with inorganic and organic acids or with alkyl halides, or, if one of the substituents has acidic properties, they can be reacted with inorganic and organic bases to give salts. The present invention also relates to such salts, to the extent that they are agriculturally acceptable.

Isoxazole(isothiazole)-5-carboxamides which are preferred herbicidal active ingredients are those of the formula Ia, where R³ is hydrogen.

Other compounds of the formula Ia which are preferred active ingredients are those in which X is oxygen or sulfur, R¹ is hydrogen or C₁ -C₄ -alkyl, R² is COYR⁵, R³ is hydrogen and R⁴ is C₁ -C₄ -alkyl or C₃ -C₈ -cycloalkyl. In these compounds, R⁵ is preferably hydrogen, C₁ -C₄ -alkyl, or phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio or halogen, or a radical ##STR6## where R⁸ and R⁹ in turn are preferably each C₁ -C₄ -alkyl.

Isoxazole(isothiazole)-5-carboxamides of the formula ##STR7## where X, R¹, R², R³ and R⁴ have the meanings stated for formula Ia, with the proviso that X is sulfur when R¹ is CH₃, R² is COOH or COOC₂ H₅ and R³ and R⁴ are each hydrogen, and that X is oxygen when R¹ is hydrogen, R² is COOH or CONH₂ and R³ and R⁴ are each hydrogen, are novel.

The isoxazole(isothiazole)-5-carboxamides of the formula I or Ia can be prepared by the following methods:

1. A process for the preparation of compounds of the formula Ib and Ia, where R² is COOR⁵ and R³ is hydrogen or C₁ -C₈ -alkyl (cf. Scheme 1), is based on the reaction of a dialkyl isoxazole- or isothiazole-4,5-dicarboxylate II (R⁸ =C₁ -C₈ -alkyl) with an aqueous base and subsequent reaction with a mineral acid to give a carboxylic acid III. Particularly suitable dicarboxylates II are lower alkyl esters (R⁵ =R⁸ =C₁ -C₄ -alkyl), dimethyl and diethyl esters being particularly preferred.

The reaction is carried out by treating a dialkyl dicarboxylate II with a strong base for example NaOH, KOH or Ca(OH)₂, at from about 0° to 80° C., preferably from 0° to 50° C., in an organic solvent, e.g. methanol or ethanol. In general, about one equivalent of the strong base is used in aqueous solution. When the reaction is complete, the mixture is cooled and acidified with a strong mineral acid, for example hydrochloric acid or sulfuric acid. The resulting carboxylic acid III can be isolated in a conventional manner, for example by filtration under suction or by extraction with an organic solvent.

To convert the carboxylic acid III into the carbonyl halide IV, the acid III is reacted in a conventional manner with an inorganic acid halide, such as thionyl chloride, a phosphorus trihalide or a phosphorus pentahalide, the chlorides being preferred. Advantageously, the inorganic acid halide is used in a n amount of from 1 to 5, preferably from 1 to 2, molar equivalents. The reaction can be carried out in the absence of a solvent or in the presence of an inert organic solvent, for example benzene or toluene, at from room temperature to the boiling point of the inorganic acid halide or of the inert organic solvent. In some cases, the addition of a catalyst, such as dimethylformamide or 4-dimethylaminopyridine, may be advantageous. When the reaction is complete, the acyl halide IV can be isolated in a conventional, manner, for example by distilling off the excess inorganic acid halide and the organic solvent and then distilling the acyl chloride IV under atmospheric or reduced pressure.

The carboxamides Ib are obtained from the carbonyl halides by reaction with an amine V. For this purpose, it is advantageous if the carbonyl halide, in an inert organic solvent, such as dichloroethane, or an ether, such as diethyl ether or methyl tert-butyl ether, is reacted with an amine V, likewise dissolved in an organic solvent. The amine V is advantageously used in from 2 to 5, preferably from 2 to 3, times the molar amount in order to bind the resulting hydrogen halide. The reaction may also be carried out in the presence of an auxiliary base, such as a tertiary amine, e.g. triethylamine. In this case, from 1 to 1.5 molar equivalents of amine V are sufficient. The reaction temperature may be from 0° to 50° C., preferably from 0° to 20° C. The reaction is generally complete after from 1 to 12 hours. The mixture can be worked up in a conventional manner, for example by hydrolysis with water and extraction of the product of the formula Ib with an organic solvent and evaporation of the organic solvent. The product of the formula Ib can be purified, for example, by recrystallization or chromatography.

The 4-alkoxycarbonylisoxazole-5-carboxamides or 4-alkoxycarbonylisothiazole-5-carboxamides Ib can be converted into the free carboxylic acids Ic by reaction with an aqueous base followed by reaction with a mineral acid. The reaction is carried out by treating the esters Ib, in an organic solvent, e.g. methanol or ethanol, with a base, e.g. NaOH, KOH or Ca(OH)₂, at from 0° to 80° C., preferably from 0° to 50° C. In general, about 1-3, preferably 1-1.5, equivalents of the strong base are used in aqueous solution. When the reaction is complete, the mixture is acidified with a strong mineral acid, for example hydro-chloric acid or sulfuric acid, while cooling. The resulting carboxylic acids Ic can be isolated by filtration under suction or by extraction with an organic solvent and evaporation of this organic solvent. The acids Ic may be further purified by recrystallizing or chromatographing them. ##STR8##

The dialkyl isoxazole- and isothiazole-4,5-dicarboxylates II required as starting materials for this process are known from the literature (J. Org. Chem. 43 (1978), 3736; Chem. Pharm. Bull. 28 (1980), 3296; Tetrahedron 30 (1974), 1365); those which are unknown can be prepared by methods generally known from the literature.

2. A further process for the preparation of the compounds Id is based on the reaction of an isoxazole- or isothiazole-5-carbonyl halide VI with an amine V. Preferred carbonyl halides VI are the chlorides. In this procedure, it is advantageous to react the carbonyl halide, in an inert organic solvent, such as dichloromethane, or an ether, such as diethyl ether or methyl tert-butyl ether, with an amine V, likewise dissolved in an organic solvent. The amine V is advantageously used in from 2 to 5, preferably from 2 to 3, times the molar amount in order to bind the resulting hydrogen halide. The reaction may also be carried out in the presence of an auxiliary base, for example a tertiary amine (triethylamine). In this case, from 1 to 1.5 molar equivalents of amine V are sufficient. The reaction temperature may be from 0° to 50° C., preferably from 0° to 20° C. The reaction is generally complete after from 1 to 12 hours. The mixture can be worked up in a conventional manner, for example by hydrolysis with water and extraction of the product VII with an organic solvent and evaporation of the organic solvent.

The isoxazole- or isothiazolecarboxamides VII are converted into the 5-aminocarbonylisoxazole-4-carboxylic acids or 5-aminocarbonylisothiazole-4-carboxylic acids of the formula Id by reaction with an alkyllithium, preferably with the addition of a solvent which is inert under the reaction conditions, such as diethyl ether or tetrahydrofuran. As a rule, the reaction is carried out under a nitrogen atmosphere at from -70° C. -80° C. In this process, the alkyllithium compound is generally used in from 2 to 3 times the molar amount, based on amide of the formula VII used. When the reaction is complete, the mixture is treated with carbon dioxide, preferably in an inert solvent, such as diethyl ether or, for example, tetrahydrofuran, the desired products of the formula Id, where R² is carboxyl, being obtained.

Using the same process, it is also possible to obtain isoxazole- and isothiazolecarboxamides of the formula, Id, where R² is formyl, if dimethylformamide is used instead of the carbon dioxide. Working up in a conventional manner gives substituted 4-formylisoxazole-5-carboxamides or 4-formylisothiazole-5-carboxamides of the formula Id. ##STR9##

The isoxazole- and isothiazole-5-carbonyl halides VI required as starting materials for this process are known from the literature. Those which are unknown can be prepared from the corresponding carboxylic acids VIII in a conventional manner, as described above. ##STR10##

The carboxylic acids VIII required for this purpose are likewise known from the literature (Chem. Ber. 106 (1973), 3345, J. Chem. Soc. 1959, 3061, J. Chem. Soc. 1963, 2032, Adv. in Heterocyclic Chem. 14 (1972), 1); those which are unknown can be prepared by methods generally known from the literature, for example from the corresponding alcohols or aldehydes by oxidation or from the corresponding nitriles by hydrolysis.

3. Another process leads to compounds Ie, in which R² is COOR⁵ and R⁵ is C₁ -C₈ -alkyl which is unsubstituted or substituted by C₁ -C₄ -alkoxy, C₁ -C₄ -alkoxy-C₁ -C₄ -alkoxy, halogen, C₁ -C₄ -alkylthio, C₁ -C₄ -alkylsulfinyl, C₁ -C₄ -alkylsulfonyl, C₁ -C₄ -alkoxycarbonyl or benzyloxy or by phenyl which may be substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano, or R⁵ is C₃ -C₆ -cycloalkyl or is C₃ -C₈ -alkenyl which is unsubstituted or substituted by phenyl which may be substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano, or R⁵ is C₃ -C₈ -alkynyl, C₆ - or C₇ -cycloalkylimino, succinimido or a radical of the formula ##STR11## by reaction of an acid Ic with a corresponding alcohol IX in the presence of a strong mineral acid, for example hydrochloric acid or sulfuric acid, at from 0° to 100° C. preferably from 20° to 50° C. As a rule, an excess of the alcohol IX is used, but it is also possible to employ an inert solvent. ##STR12##

4. In a further process for the preparation of the compounds of the formula Ie, an acid Ic is reacted with an alcohol or thiol IX in the presence of a dehydrating agent (e.g. dicyclohexylcarbodiimide (DCC)) at from -20° to 50° C., preferably from 0° to 30° C. As a rule, the starting materials are used for the reaction in a roughly stoichiometric amount. The reaction is preferably carried out in the presence of an inert solvent, for example tetrahydrofuran, dichloromethane or toluene. ##STR13## (where Y is O or S).

5. Another process for the preparation of the compounds Ic is based on the reaction of an alkyl carboxylate If with an alkali metal alkoxide X, such as sodium alkoxide or potassium alkoxide, with a corresponding alcohol IX in a conventional manner at from 20° C. to the boiling point of the selected alcohol IX. ##STR14## (R⁹ =methyl or ethyl)

6. Compounds of the formula Ig, where R² is COOR² and R⁵ is a salt-forming cation, for example an alkali metal, alkaline earth metal, ammonium or substituted ammonium ion, are obtained by reacting a substituted isoxazole- or isothiazole-4-carboxylic acid Ic with one equivalent of the salt-forming cation. If the cation in question is an inorganic cation, for example sodium, potassium or calcium, the acid Ic is advantageously dissolved or suspended in water or in a lower alcohol or a mixture of these, and one equivalent of the salt-forming cation is added. The salt-forming cation may be used, for example, in the form of its hydroxide, carbonate or bicarbonate, preferably in the form of its hydroxide. The reaction is generally complete after a few minutes, and the mixture can be worked up in a conventional manner, for example by precipitation and filtration under suction or by evaporation of the solvent. To prepare compounds Ig in which B.sup.⊕ is ammonium or organic ammonium, the acid Ic is dissolved or suspended in an organic solvent, e.g. diethyl ether, tetrahydrofuran or dioxane, and the mixture is treated with one equivalent of ammonia, an amine or a tetraalkylammonium hydroxide.

Among the amines which may be used, the following should be mentioned: methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, sec-butylamine, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, dodecylamine, tridecylamine, tetradecylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, ethanolamines, n-propanolamine, isopropanolamine, diethanolamine, N,N-diethylethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-buten-2-ylamine, n-penten-2-ylamine, 2,3-dimethylbuten-2-ylamine, dibuten-2-ylamine, n-hexen-2-ylamine, propylenediamine, tallowamine, cyclopentylamine, cyclohexylamine, dicyclohexylamine, piperidine, morpholine and pyrrolidine.

In the case of tetraalkylammonium hydroxides, for example, tetramethyl-, tetraethyl- or trimethylbenzylammonium hydroxide may be used. As a rule, the ammonium salt or organic ammonium salt is precipitated from the solution and can be isolated by a conventional method. Alternatively, the salt of the formula Ig can also be obtained by evaporating the solvent. ##STR15##

7. Another process leads to compounds Ih in which R² is CONR⁶ R⁷. It consists in reacting an ester Ib with a primary or secondary amine XI. The process is carried out by reacting an ester Ib with from 1 to 50 times the molar amount of amine XI, in the presence or absence of an organic solvent, at from room temperature to the boiling point of the amine or of the organic solvent. Preferred esters Ib are lower alkyl esters, particularly the methyl and ethyl esters. The reaction products Ih can be isolated in a conventional manner, for example by filtration under suction or evaporation of the solution and, if required, can be further purified by recrystallization or chromatography. ##STR16##

8. In another process for the synthesis of the compounds Ib, a dialkyl isoxazole- or isothiazole-4,5-dicarboxylate II is reacted with an amine V.

Particularly suitable dialkyl esters II are lower alkyl esters, preferably dimethyl esters or diethyl esters. The reaction is carried out by treating a dialkyl dicraboxylate II with about one equivalent of a primary or secondary amine V at from 0° to 100° C., preferably from 50° to 80° C., in an organic solvent, for example an alcohol, such as methanol or ethanol. When the reaction is complete, the mixture is cooled and filtered under suction or evaporated down. The resulting product of the formula Ib can be further purified by a conventional standard method, such as recrystallization or chromatography. ##STR17##

9. Compounds of the formula Ii can be obtained by reacting a substituted isothiazole-4,5-dicarboxylic anhydride XII with an amine V. The reaction is advantageously carried out by initially taking the anhydride XII in an inert solvent, such as an ether or a halohydrocarbon, and adding dropwise about a molar amount of an amine V, if necessary likewise dissolved in an inert solvent. After the reaction is complete, the reaction product is filtered off under suction or isolated by evaporating the solvent used. In some case, the isomeric amides XIII may be formed in this process, the amide Ii generally being the preferred ones. ##STR18##

The isothiazole-4,5-dicarboxylic anhydrides XII required as starting materials for this process are known form the literature (J. Chem. Soc. 1959, 3061); those which are unknown can be synthesised by methods which are generally known from the literature.

10. In another process for the preparation of compounds of the formula Ik, an acid Ic is reacted with an alcohol or thiol XIV in the presence of a 1-methyl-2-halopyridinium iodide at from 20° to 80° C., preferably from 30° to 40° C. The reaction is carried out in the presence of an inert solvent, e.g. dichloromethane or toluene. The process is known in principle from the literature (Chem. Lett. 1045 (1975); ibid. 13 (1976); ibid. 49 (1976)).

The Examples which follow illustrate the preparation of the intermediates for the synthesis of the compounds I or Ia.

EXAMPLE a

11.7 g of aniline are added dropwise to 10.0 g of 3-ethylisoxazole-5-carbonyl chloride in 150 ml of dichloromethane, while cooling with ice. The mixture is stirred overnight at room temperature, water and concentrated hydrochloric acid are added and the organic phase is separated off, washed with sodium bicarbonate solution and evaporated down to give 11.8 g of 3-ethylisoxazole-5-carboxanilide as colorless crystals of melting point 122°-124° C.

For example, the isoxazole-5-carboxamides VII can be synthesized in a similar manner:

    ______________________________________                                          ##STR20##                   (VII)                                             R.sup.1      R.sup.4         mp. [°C.]                                  ______________________________________                                         H            i-C.sub.3 H.sub.7                                                 H            tert -C.sub.4 H.sub.9                                                                          103-106                                           H            cyclo-C.sub.3 H.sub.5                                             H            cyclo-C.sub.6 H.sub.11                                            H            C.sub.6 H.sub.5                                                   CH.sub.3     H               167-171                                           CH.sub.3     i-C.sub.3 H.sub.7                                                                              92-93                                             CH.sub.3     tert -C.sub.4 H.sub.9                                                                          55-60                                             CH.sub.3     1-Ethylcyclohexyl                                                                              oil                                               CH.sub.3     4-Methyltetrahydro-                                                                            63-65                                                          pyran-4-yl                                                        CH.sub.3     C.sub.6 H.sub.5 145-147                                           CH.sub.3     4-ClC.sub.6 H.sub.4                                                                            216-219                                           CH.sub.3     3-CF.sub.3CH.sub.6 H.sub.4                                                                     146-148                                           C.sub.2 H.sub.5                                                                             i-C.sub.3 H.sub.7                                                                              85-87                                             C.sub.2 H.sub.5                                                                             tert -C.sub.4 H.sub.9                                                                          67-70                                             C.sub.2 H.sub.5                                                                             4-ClC.sub.6 H.sub.4                                                                            170-173                                           C.sub.2 H.sub.5                                                                             3-CF.sub.3C.sub.6 H.sub.4                                                                      121-122                                           i-C.sub.3 H.sub.7                                                                           H                                                                 i-C.sub.3 H.sub.7                                                                           CH.sub.3        69-73                                             i-C.sub.3 H.sub.7                                                                           C.sub.2 H.sub.5 69-72                                             i-C.sub. 3 H.sub.7                                                                          n-C.sub.3 H.sub.7                                                                              79-80                                             i-C.sub.3 H.sub.7                                                                           i-C.sub.3 H.sub.7                                                                              122-125                                           i-C.sub.3 H.sub.7                                                                           n-C.sub.4 H.sub.9                                                                              67-68                                             i-C.sub.3 H.sub.7                                                                           sec -C.sub.4 H.sub.9                                                                           133-135                                           i-C.sub.3 H.sub.7                                                                           i-C.sub.4 H.sub.9                                                                              85-86                                             i-C.sub.3 H.sub.7                                                                           tert -C.sub.4 H.sub.9                                                                          116-118                                           i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 C.sub.2 H.sub.5                                                              118-120                                           i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 C.sub.3 H.sub.7                                                              33-34                                             i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub.3                                                   65-66                                             i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 CH.sub.2 SCH.sub.3                                                           42                                                i-C.sub.3 H.sub.7                                                                           CH.sub.2 CH.sub.2 SCH.sub.3                                       i-C.sub.3 H.sub.7                                                                           CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3                                                           34-36                                             i-C.sub.3 H.sub.7                                                                           CH.sub.2 CH.sub.2 OCH.sub.3                                                                    oil                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                                                            oil                                               i-C.sub.3 H.sub.7                                                                           cyclo-C.sub.3 H.sub.5                                                                          88-90                                             i-C.sub.3 H.sub.7                                                                           cyclo-C.sub.6 H.sub.11                                                                         152-154                                           i-C.sub.3 H.sub.7                                                                           1-Methylcyclohexyl                                                i-C.sub. 3 H.sub.7                                                                          1-Ethylcyclohexyl                                                                              50-51                                             i-C.sub.3 H.sub.7                                                                           4-Methyltetrahydro-                                                                            94-96                                                          pyran-4-yl                                                        i-C.sub.3 H.sub.7                                                                           4-Ethyltetrahydro-                                                                             50-51                                                          pyran-4-yl                                                        i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 -cycloC.sub.6 H.sub.11                                                       83                                                i-C.sub.3 H.sub.7                                                                           CH.sub.2 CHCH.sub.2                                                                            65-66                                             i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 CHCH.sub.2                                                                    99-106                                           i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 CCH                                                                          85-86                                             i-C.sub.3 H.sub.7                                                                           CH.sub.2C.sub.6 H.sub.5                                                                        79-81                                             i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2 C.sub.6 H.sub.5                                 i-C.sub.3 H.sub.7                                                                           CH.sub.2C(CH.sub.3).sub.3                                                                      87-89                                             i-C.sub.3 H.sub.7                                                                           C.sub.6 H.sub.5 106-108                                           i-C.sub.3 H.sub.7                                                                           4-ClC.sub.6 H.sub.4                                                                            176-178                                           i-C.sub.3 H.sub.7                                                                           3-CF.sub.3C.sub.6 H.sub.4                                                                      74-78                                             tert.-C.sub.4 H.sub.9                                                                       i-C.sub.3 H.sub.7                                                                              120-122                                           tert.-C.sub.4 H.sub.9                                                                       tert-C.sub.4 H.sub.9                                                                           129-133                                           tert.-C.sub.4 H.sub.9                                                                       C.sub.6 H.sub.5 121-122                                           tert.-C.sub.4 H.sub.9                                                                       4-ClC.sub.6 H.sub.4                                                                            158-161                                           tert.-C.sub.4 H.sub.9                                                                       3-CF.sub.3C.sub.6 H.sub.4                                                                      104-108                                           cyclo-C.sub.6 H.sub.11                                                                      i-C.sub.3 H.sub.7                                                                              139-140                                           cyclo-C.sub.6 H.sub.11                                                                      tert -C.sub.4 H.sub.9                                                                          121-122                                           cyclo-C.sub.6 H.sub.11                                                                      cyclo-C.sub.3 H.sub.5                                                                          144-146                                           cyclo-C.sub.6 H.sub.11                                                                      cyclo-C.sub.6 H.sub.11                                            cyclo-C.sub.6 H.sub.11                                                                      C.sub.6 H.sub.5 180-181                                           Tetrahydropyran-3-yl                                                                        i-C.sub.3 H.sub.7                                                                              102-104                                           Tetrahydropyran-3-yl                                                                        tert -C.sub.4 H.sub.9                                                                          110-114                                           Tetrahydropyran-3-yl                                                                        cyclo-C.sub.3 H.sub.5                                                                          108-110                                           Tetrahydropyran-3-yl                                                                        cyclo-C.sub.6 H.sub.11                                            Tetrahydropyran-3-yl                                                                        C.sub.6 H.sub.5 149-151                                           C.sub.6 H.sub.5                                                                             i-C.sub.3 H.sub.7                                                 C.sub.6 H.sub.5                                                                             tert -C.sub.4 H.sub.9                                             C.sub.6 H.sub.5                                                                             cyclo-C.sub.3 H.sub.5                                             C.sub.6 H.sub.5                                                                             cyclo-C.sub.6 H.sub.11                                            C.sub.6 H.sub.5                                                                             C.sub.6 H.sub.5                                                   4-ClC.sub.6 H.sub.4                                                                         i-C.sub.3 H.sub.7                                                                              166-171                                           4-ClC.sub.6 H.sub.4                                                                         tert -C.sub.4 H.sub.9                                                                          128-132                                           4-ClC.sub.6 H.sub.4                                                                         C.sub.6 H.sub.5 229-232                                           4-ClC.sub.6 H.sub.4                                                                         4-ClC.sub.6 H.sub.4                                               4-ClC.sub.6 H.sub.4                                                                         3-CF.sub.3C.sub.6 H.sub.4                                                                      163-165                                           cyclo-C.sub.3 H.sub.5                                                                       i-C.sub.3 H.sub. 7                                                                             114-117                                           cyclo-C.sub.3 H.sub.5                                                                       tert -C.sub.4 H.sub.9                                                                          106-107                                           cyclo-C.sub.3 H.sub.5                                                                       C.sub.6 H.sub.5 180-186                                           ______________________________________                                                                      mp. [°C.]/                                                              .sup.1 H.NMR                                      R.sup.1      R.sup.4         (CDCl.sub.3) [ppm]                                ______________________________________                                         i-C.sub.3 H.sub.7                                                                           cyclo-C.sub.5 H.sub.9                                                                          119-121                                           i-C.sub.3 H.sub.7                                                                           Tetrahydrofur-3-yl                                                                             75-78                                             i-C.sub.3 H.sub.7                                                                           Thiazol-2-yl    165-168                                           i-C.sub.3 H.sub.7                                                                           5-Methylthiazol2-yl                                                                            149-153                                           i-C.sub.3 H.sub.7                                                                           5-Ethylthiazol2-yl                                                                             157-163                                           i-C.sub.3 H.sub.7                                                                           5-n-Propylthiazol-yl                                                                           140-145                                           i-C.sub.3 H.sub.7                                                                           CH(CH.sub.3)CH.sub.2 CN                                                                        88-92                                             i-C.sub.3 H.sub.7                                                                           C(CH.sub.3).sub.2CH.sub.2 CN                                                                   95-97                                             i-C.sub.3 H.sub.7                                                                           OC.sub.2 H.sub.5                                                                               33-35                                             i-C.sub.3 H.sub.7                                                                           Pyrid-2-yl      104-106                                           i-C.sub.3 H.sub.7                                                                           Pyrid-3-yl      150-152                                           i-C.sub.3 H.sub.7                                                                           Pyrid-4-yl      185-187                                           i-C.sub.3 H.sub.7                                                                           Pyrimid-2-yl    94-99                                             n-C.sub.3 H.sub.7                                                                           i-C.sub.3 H.sub.7                                                                              108-110                                           n-C.sub.3 H.sub.7                                                                           cyclo-C.sub.3 H.sub.5                                                                          104-106                                           n-C.sub.3 H.sub.7                                                                           tert -C.sub.4 H.sub.9                                                                          85-86                                             n-C.sub.3 H.sub.7                                                                           C.sub.6 H.sub.5 118-119                                           n-C.sub.3 H.sub. 7                                                                          cyclo-C.sub.6 H.sub.11                                                                         136-137                                           s-C.sub.4 H.sub.9                                                                           i-C.sub.3 H.sub.7                                                                              150-152                                           s-C.sub.4 H.sub.9                                                                           cyclo-C.sub.3 H.sub.5                                                                          107-111                                           s-C.sub.4 H.sub.9                                                                           tert -C.sub.4 H.sub.9                                                                          138-142                                           s-C.sub.4 H.sub.9                                                                           C.sub.6 H.sub.5  99-101                                           i-C.sub.3 H.sub.7                                                                           N(CH.sub.3).sub.2                                                                              131-133                                           CH.sub.3     N(CH.sub.3).sub.2                                                                              111-113                                           CH.sub.3     Morpholino      190-192                                           CH.sub.3     Piperidino      158-161                                           CH.sub.3     CH.sub.3        146-148                                           i-C.sub.3 H.sub.7                                                                           Piperidino      133-135                                           i-C.sub.3 H.sub.7                                                                           Morpholino      178-179                                           CH.sub.3     C.sub.2 H.sub.5 97-99                                             neo-C.sub.5 H.sub.11                                                                        CH.sub.3        128-130                                           neo-C.sub.5 H.sub.11                                                                        i-C.sub.3 H.sub.7                                                                              85-88                                             neo-C.sub.5 H.sub.11                                                                        cyclo-C.sub.3 H.sub.5                                                                          109-112                                           neo-C.sub.5 H.sub.11                                                                        tert -C.sub.4 H.sub.9                                                                          97-99                                             neo-C.sub.5 H.sub.11                                                                        C.sub.6 H.sub.5 137-140                                           n-C.sub.4 H.sub.9                                                                           CH.sub.3        74-76                                             n-C.sub.4 H.sub.9                                                                           i-C.sub.3 H.sub.7                                                                               97-100                                           n-C.sub.4 H.sub.9                                                                           cyclo-C.sub.3 H.sub.5                                                                          82-86                                             n-C.sub.4 H.sub.9                                                                           tert -C.sub.4 H.sub.9                                                                          60-64                                             n-C.sub.4 H.sub.9                                                                           C.sub.6 H.sub.5 113-120                                           cyclo-C.sub.5 H.sub.9                                                                       tert -C.sub.4 H.sub.9                                                                          114-115                                           cyclo-C.sub.5 H.sub.9                                                                       CH.sub.3        88-89                                             cyclo-C.sub.5 H.sub.9                                                                       cyclo-C.sub.3 H.sub.5                                                                          108-109                                           cyclo-C.sub.5 H.sub.9                                                                       C.sub.6 H.sub.5 146-148                                           n-C.sub.4 H.sub.9                                                                           OCH.sub.3       62-66                                             CH.sub.3OCH.sub.2                                                                           tert -C.sub.4 H.sub.9                                                                          50-55                                             CH.sub.3OCH.sub.2                                                                           cyclo-C.sub.3 H.sub.5                                                                          55-60                                             2-Methoxyphenyl                                                                             tert -C.sub.4 H.sub.9                                                                          119-120                                           2-Methoxyphenyl                                                                             cyclo-C.sub.3 H.sub.5                                                                          160-163                                           i-C.sub.3 H.sub.7                                                                           CH.sub.2 -cyclo-C.sub.3 H.sub.5                                                                77-80                                             n-C.sub.4 H.sub.9                                                                           CH.sub.2 -cyclo-C.sub.3 H.sub.5                                                                102-105                                           CH.sub.3 OCH(CH.sub.3)                                                                      tert -C.sub.4 H.sub.9                                                                          76-79                                             cyclo-C.sub.3 H.sub.5                                                                       cyclo-C.sub.5 H.sub.9                                                                          148-149                                           2,6-Difluorophenyl                                                                          tert -C.sub.4 H.sub.9                                                                          118-122                                           2,6-Difluorophenyl                                                                          cyclo-C.sub.3 H.sub.5                                                                          128-132                                           CH.sub.3     cyclo-C.sub.4 H.sub.7                                                                          114-115                                           i-C.sub.3 H.sub.7                                                                           cyclo-C.sub.4 H.sub.7                                                                          84-85                                             CH.sub.3 O   tert -C.sub.4 H.sub.9                                                                          65-68                                             ______________________________________                                          ##STR21##                   (VII)                                             R.sup.1     R.sup.3    R.sup.4                                                                               pm. [°C.]                                 ______________________________________                                         i-C.sub.3 H.sub.7                                                                          CH.sub.3   CH.sub.3                                                i-C.sub.3 H.sub.7                                                                          C.sub.2 H.sub.5                                                                           C.sub.2 H.sub.5                                                                       oil                                              ______________________________________                                    

EXAMPLE b

65 g of diethyl 3-methylisoxazole-4,5-dicarboxylate, dissolved in 100 ml of ethanol, are added dropwise to 18.9 g of potassium hydroxide in 100 ml of water at room temperature. After 16 hours, the mixture is poured onto 300 ml of water and extracted with ether, and the aqueous phase is acidified with concentration hydrochloric acid. Extracting with dichloromethane and evaporating down give 3-methyl-4-ethoxycarbonylisoxazole-5-carboxylic acid as colorless crystals of melting point 54°-58° C.

EXAMPLE c

A solution of 14.9 g of NaOH in 120 ml of water and 150 ml of methanol is added dropwise to 85.5 g of dimethyl 3-ethylisothiazole-4,5-dicarboxylate in 300 ml of methanol, while cooling with ice. After 2 hours, the mixture is evaporated down, 1.5 l of water are added to the residue and the mixture is stirred, and extracted with ether. The aqueous phase is acidified with concentrated hydrochloric acid and extracted by shaking with dichloromethane. The organic phases are evaporated down to give 76.4 g of 3-ethyl-4-methoxycarbonylisothiazole-5-carboxylic acid of melting point 43°-45° C.

For example, the isoxazole(isothiazole)-5-carboxylic acids III can be synthesized similarly to Examples b and c.

    ______________________________________                                          ##STR22##                    (III)                                            R.sup.1          R.sup.5  X     mp. [°C.]                               ______________________________________                                         H                CH.sub.3 O                                                    H                C.sub.2 H.sub.5                                                                         O                                                    H                CH.sub.3 S                                                    H                C.sub.2 H.sub.5                                                                         S                                                    CH.sub.3         CH.sub.3 O                                                    CH.sub.3         CH.sub.3 S     75-81                                          CH.sub.3         C.sub.2 H.sub.5                                                                         S                                                    C.sub.2 H.sub.5  CH.sub.3 O                                                    C.sub.2 H.sub.5  C.sub.2 H.sub.5                                                                         O                                                    C.sub.2 H.sub.5  C.sub.2 H.sub.5                                                                         S                                                    n-C.sub.3 H.sub.7                                                                               CH.sub.3 O                                                    n-C.sub.3 H.sub.7                                                                               C.sub.2 H.sub.5                                                                         O                                                    n-C.sub.3 H.sub.7                                                                               CH.sub.3 S                                                    n-C.sub.3 H.sub.7                                                                               C.sub.2 H.sub.5                                                                         S                                                    i-C.sub.3 H.sub.7                                                                               CH.sub.3 O                                                    i-C.sub.3 H.sub.7                                                                               C.sub.2 H.sub.5                                                                         O                                                    i-C.sub.3 H.sub.7                                                                               CH.sub.3 S     oil                                            i-C.sub.3 H.sub.7                                                                               C.sub.2 H.sub.5                                                                         S                                                    s-C.sub.4 H.sub.9                                                                               CH.sub.3 O                                                    s-C.sub.4 H.sub.9                                                                               C.sub.2 H.sub.5                                                                         O                                                    s-C.sub.4 H.sub.9                                                                               CH.sub.3 S                                                    s-C.sub.4 H.sub.9                                                                               C.sub.2 H.sub.5                                                                         S                                                    tert -C.sub.4 H.sub.9                                                                           CH.sub.3 O                                                    tert -C.sub.4 H.sub.9                                                                           C.sub.2 H.sub.5                                                                         O                                                    tert -C.sub.4 H.sub.9                                                                           CH.sub.3 S                                                    tert -C.sub.4 H.sub.9                                                                           C.sub.2 H.sub.5                                                                         S                                                    cyclo-C.sub.3 H.sub.5                                                                           CH.sub.3 O                                                    cyclo-C.sub.3 H.sub.5                                                                           C.sub.2 H.sub.5                                                                         O                                                    cyclo-C.sub.3 H.sub.5                                                                           CH.sub.3 S                                                    cyclo-C.sub.3 H.sub.5                                                                           C.sub.2 H.sub.5                                                                         S                                                    cyclo-C.sub.6 H.sub.11                                                                          CH.sub.3 O                                                    cyclo-C.sub.6 H.sub.11                                                                          C.sub.2 H.sub.5                                                                         O                                                    cyclo-C.sub.6 H.sub.11                                                                          CH.sub.3 S                                                    cyclo-C.sub.6 H.sub.11                                                                          C.sub.2 H.sub.5                                                                         S                                                    Tetrahydropyran-3-yl                                                                            CH.sub.3 O                                                    Tetrahydropyran-3-yl                                                                            C.sub.2 H.sub.5                                                                         O                                                    Tetrahydropyran-3-yl                                                                            CH.sub.3 S                                                    Tetrahydropyran-3-yl                                                                            C.sub.2 H.sub.5                                                                         S                                                    C.sub.6 H.sub.5  CH.sub.3 O                                                    C.sub.6 H.sub.5  C.sub.2 H.sub.5                                                                         O                                                    C.sub.6 H.sub.5  CH.sub.3 S     139-141                                        C.sub.6 H.sub.5  C.sub.2 H.sub.5                                                                         S                                                    ______________________________________                                    

PREPARATION EXAMPLES FOR COMPOUNDS I AND Ia EXAMPLE 1

2.9 g of isopropylamine are added dropwise to 10 g of diethyl 3-methylisoxazole-4,5-dicarboxylate, dissolved in 100 ml of methanol, and the mixture is then refluxed. After 7 hours, the mixture is evaporated down and the remaining oil is chromatographed over silica gel (using 9:1 toluene/acetone). Methyl 5-isopropylaminocarbonyl-3-methylisoxazole-4-carboxylate is obtained as colorless crystals of melting point 64°-66° C. (compound No. 1005).

EXAMPLE 2

2.6 g of the ester from Example 1 and 0.8 g of potassium hydroxide in 20 ml of water and 20 ml of ethanol are stirred for 16 hours at room temperature. Thereafter, the mixture is diluted with water, acidified with concentrated hydrochloric acid and extracted by shaking with dichloromethane. Evaporating down gives 1.8 g of 5-isopropylaminocarbonyl-3-methylisoxazole-4-carboxylic acid as colorless crystals of melting point 86°-92° C. (compound No. 1004).

EXAMPLE 3

70 ml of n-butyllithium (1.6 molar solution in n-hexane) are added dropwise, at -70° C., to 9.0 g of the anilide from Example a, dissolved in 200 ml of absolute tetrahydrofuran. Stirring is carried out for half an hour and the reaction mixture is poured onto 500 g of solid carbon dioxide. After standing overnight, the mixture is evaporated down and the residue is partitioned between H₂ O, sodium hydroxide solution and ethyl acetate. By evaporating down the ethyl acetate phase, 2.0 g of starting material can be recovered. Acidification of the aqueous phase with concentrated hydrochloric acid and filtration under suction give 8.30 g of 5-anilinocarbonyl-3-ethylisoxazole-4-carboxylic acid as colorless crystals of melting point 150°-152° C. (compound No. 1015).

EXAMPLE 4

5.0 g of 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylic acid are dissolved in 200 ml of methanol, and 5 ml of concentrated H₂ SO₄ are added. After 2 days, the mixture is evaporated down, the residue is partitioned between ethyl acetate and water and the organic phase is evaporated down. 4.0 g of methyl 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylate are obtained as a colorless oil (compound No. 1007).

H-NMR (CDCl₃): d=1.48 (s; 9H), 2.50 (s; 3H), 3.99 (s; 1H), 9.42 (bs; 1H, NH).

EXAMPLE 5 a) 3-Ethyl-4-methoxycarbonylisothiazole-5-carbonyl chloride

73 g of the carboxylic acid from Example c and 80 g of thionyl chloride in 200 ml of toluene are refluxed in the presence of a little dimethylformamide until the evolution of gas is complete. The crude carbonyl chloride which remains in quantitative yield after evaporation is directly reacted further.

b) Methyl 5-isopropylaminocarbonyl-3-ethylisothiazole-4-carboxylate

8.4 g of isopropylamine are slowly added dropwise to 16.5 g of the crude acyl chloride from a) in 200 ml of dichloromethane, while cooling with ice. Stirring is carried out overnight, hydrolysis is effected with 150 ml of water and the organic phase is separated off, washed with bicarbonate solution, dilute hydrochloric acid and water and then evaporated down. 16.2 g of methyl 5-isopropylaminocarbonyl-3-ethylthiazole-4-carboxylate of melting point 55°-56° C. (compound No. 3007) are obtained.

EXAMPLE 6

2.8 g of KOH in 30 ml of water are added to 11 g of the ester from Example 5 in 50 ml of ethanol, and the mixture is stirred overnight at room temperature. It is diluted with 150 ml of water and extracted with ether, and the aqueous phase is acidified with concentrated hydrochloric acid. Extraction by shaking with dichloromethane and evaporation give 10 g of 5-isopropylaminocarbonyl-3-ethylisothiazole-4-carboxylic acid of melting point 138°-140° C. (compound 3006).

EXAMPLE 7

4.0 g of methyl 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylate and 50 ml of concentrated ammonia are refluxed for 3 hours. After cooling, the mixture is diluted with water and extracted with dichloromethane and the organic phase is evaporated down. 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxamide is obtained as colorless crystals of melting point 155°-158° C. (compound No. 1).

EXAMPLE 8

56 ml of butyllithium (1.6 molar solution in n-hexane) are added dropwise, at -78° C., to 8 g of the tert-butylamine of 3-methylisoxazole-5-carboxylic acid in 150 ml of tetrahydrofuran. The mixture is stirred for 1 hour, after which 22 ml of dimethylformamide are slowly added dropwise. The mixture is allowed to reach room temperature overnight and is hydrolyzed with water, neutralized with concentrated hydrochloric acid and extracted with ether. The oil which remains after evaporation is chromatographed over silica gel using cyclohexane/ethyl acetate. The tert-butylamide of 4-formyl-3-methylisoxazole-5-carboxylic acid is obtained as the first fraction, in the form of pale yellow crystals of melting point 36°-38° C. (compound No. 2).

EXAMPLE 9 a) 3-Methyl-4-ethoxycarbonylisoxazole-5-carbonylchloride

13.3 g of the carboxylic acid from Example b and 20 ml of thionyl chloride are refluxed in the presence of a little dimethylformamide until the evolution of gas is complete. The crude carbonyl chloride which remains in quantitative yield after evaporation is directly reacted further.

b) 3.4 g of diethylamine are slowly added dropwise to 5 g of the crude acyl chloride from a) in 100 g of dichloromethane, while cooling with ice. Stirring is carried out overnight, hydrolysis is effected with water and the organic phase is separated off, washed with bicarbonate and then evaporated down. 5.0 g of ethyl 5-diethylaminocarbonyl-3-methylisoxazole-4-carboxylate are obtained as a brown oil (compound No. 3).

H-NMR (CDCl₃): δ=1.15 (t; 3H), 1.27 and 1.31 (2t; 6H), 2.50 (s; 3H), 3.17 (q; 2H), 3.58 (q; 2H), 4.28 (q; 2H).

EXAMPLE 10

5.0 g of the ester from Example 9 and 1.4 g of potassium hydroxide in 10 ml of water and 20 ml of ethanol are stirred at room temperature. When the reaction is complete, the mixture is diluted with water and extracted with dichloromethane. Thereafter, the aqueous phase is acidified with hydrochloric acid and extracted with dichloromethane, and the organic phase is evaporated down. 3.0 g of 5-diethylaminocarbonyl-3-methylisoxazole-4-carboxylic acid are obtained as a pale oil (compound No. 4).

H-NMR (CDCl₃): δ=1.28 and 1.32 (2t; 6H), 2.60 (s; 3H), 3.59 and 3.62 (2q; 4H), 10.50 (bs; 1H, COOH).

EXAMPLE 11

A mixture of 1.2 g of 2-methylpropane-2-thiol, 3.0 g of 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylic acid and 5.9 g of tri-n-butylamine in 20 ml of dichloromethane is added dropwise to a stirred suspension of 4.1 g of 1-methyl-2-chloropyridinium iodide in 40 ml of dichloromethane at room temperature. The mixture is refluxed for 3 hours, the solvent is stripped off under reduced pressure and the crude product is purified by column chromatography over silica gel. 2.1 g of the tert-butyl thioester of 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylic acid are obtained as a yellow oil (compound No. 2003).

For example, the compounds mentioned in Tables 1 to 3 below can be prepared similarly to Examples 1 to 10.

                                      TABLE 1                                      __________________________________________________________________________      ##STR23##                                                                                                                 mp [°C.]/.sup.1 H-NMR       No. R.sup.1      R.sup.5         R.sup.4    (CDCl.sub.3)                       __________________________________________________________________________                                                 [ppm]                              1001                                                                               H            H               i-C.sub.3 H.sub.7                             1002                                                                               H            H               tert.-C.sub.4 H.sub.9                                                                     oil 1.55(s; 9H),                                                               7.50 (bs; 1H,                                                                  NH), 8.78(s; 1H)                   1003                                                                               CH.sub.3     H               H          266-268                            1004                                                                               CH.sub.3     H               i-C.sub.3 H.sub.7                                                                          86-92                             1005                                                                               CH.sub.3     CH.sub.3        i-C.sub.3 H.sub.7                                                                          64-66                             1006                                                                               CH.sub.3     H               tert.-C.sub.4 H.sub.9                                                                      92-94                             1007                                                                               CH.sub.3     CH.sub.3        tert.-C.sub.4 H.sub.9                         1008                                                                               CH.sub.3     H               1-ethylcyclohexyl                                                                         119-121                            1009                                                                               CH.sub.3     H               4-methyltetrahydro-                                                                        80-87                                                              pyran-4-yl                                    1010                                                                               CH.sub.3     H               C.sub.6 H.sub.5                                                                           204-210                            1011                                                                               CH.sub.3     H               4-ClC.sub.6 H.sub.4                                                                       233-237                            1012                                                                               CH.sub.3     H               3-CF.sub.3C.sub.6 H.sub.4                                                                 188- 191                           1013                                                                               C.sub.2 H.sub.5                                                                             H               i-C.sub.3 H.sub.7                                                                          63-66                             1014                                                                               C.sub.2 H.sub.5                                                                             H               tert.-C.sub.4 H.sub.9                                                                      53-58                             1015                                                                               C.sub.2 H.sub.5                                                                             H               C.sub.6 H.sub.5                                                                           150-152                            1016                                                                               C.sub.2 H.sub.5                                                                             H               4-ClC.sub.6 H.sub.4                                                                       193-196                            1017                                                                               C.sub.2 H.sub.5                                                                             H               3-CF.sub.3C.sub.6 H.sub.4                                                                 160-162                            1018                                                                               i-C.sub.3 H.sub.7                                                                           H               H                                             1019                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.3   147-148                            1020                                                                               i-C.sub.3 H.sub.7                                                                           H               C.sub.2 H.sub.5                                                                           100-101                            1021                                                                               i-C.sub.3 H.sub.7                                                                           H               n-C.sub.3 H.sub.7                                                                          85-86                             1022                                                                               i-C.sub.3 H.sub.7                                                                           H               i-C.sub.3 H.sub.7                                                                          98-99                             1023                                                                               i-C.sub.3 H.sub.7                                                                           H               n-C.sub.4 H.sub.9                                                                          96-97                             1024                                                                               i-C.sub.3 H.sub.7                                                                           H               i-C.sub.4 H.sub.9                                                                         112-114                            1025                                                                               i-C.sub.3 H.sub.7                                                                           H               sec-C.sub.4 H.sub.9                                                                       oil 1.00(t; 3H),                                                               1.32(d; 3H),                                                                   1.37(d; 6H),                                                                   1.64(quint;                                                                    2H), 3.78(sept;                                                                1H), 4.15                                                                      (m; 1H), 7.00                                                                  (bs; 1H,NH)                        1026                                                                               i-C.sub.3 H.sub.7                                                                           H               tert.-C.sub.4 H.sub.9                                                                      94-98                             1027                                                                               i-C.sub.3 H.sub.7                                                                           H               C(CH.sub.3).sub.2 C.sub.2 H.sub.5                                                          44-46                             1028                                                                               i-C.sub.3 H.sub.7                                                                           H               C(CH.sub.3).sub.2 C.sub.3 H.sub.7                                                          52-53                             1029                                                                               i-C.sub.3 H.sub.7                                                                           H               C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).su                                      b.3         89-91                             1030                                                                               i-C.sub.3 H.sub.7                                                                           H               C(CH.sub.3).sub.2 CH.sub.2 SCH.sub.3                                                      oil 1.35(d; 3H),                                                               1.56(s; 6H),                                                                   2.18(s; 3H),                                                                   2.99(s; 2H),                                                                   3.77(sept; 1H),                                                                7.30(bs; 1H, NH)                   1031                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 CH.sub.2 SCH.sub.3                   1032                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3                                                      116-118                            1033                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 CH.sub.2 OCH.sub.3                                                                69-71                             1034                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2           1035                                                                               i-C.sub.3 H.sub.7                                                                           H               cyclo-C.sub.3 H.sub.5                                                                      74-76                             1036                                                                               i-C.sub.3 H.sub.7                                                                           H               cyclo-C.sub.6 H.sub.11                                                                    112-114                            1037                                                                               i-C.sub.3 H.sub.7                                                                           H               1-ethylcyclohexyl                                                                          89-90                             1038                                                                               i-C.sub.3 H.sub.7                                                                           H               4-methyltetrahydro-                                                                       129-130                                                             pyran-4-yl                                    1039                                                                               i-C.sub.3 H.sub.7                                                                           H               1-C(CH.sub.3).sub.2 -cycloC.sub.6                                              H.sub.11   144-146                            1040                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 CHCH.sub.2                                                                        92-94                             1041                                                                               i-C.sub.3 H.sub.7                                                                           H               C(CH.sub.3).sub.2 CHCH.sub.2                                                              oil; 1.35(d; 6H),                                                              1.62(s; 6H),                                                                   3.78(sept; 1H),                                                                5.20(d; 1H),                                                                   5.25(d; 1H),                                                                   6.10(dd; 1H),                                                                  7.10(bs; 1H, NH)                   1042                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 C.sub.6 H.sub.5                                                                  oil 1.30(d; 6H),                                                               3.74(sept; 1H),                                                                4.70(d; 2H),                                                                   7.35(bs; 5H),                                                                  7.85(bt; 1H, NH)                   1043                                                                               i-C.sub.3 H.sub.7                                                                           H               C(CH.sub.3).sub.2 C.sub.6 H.sub.5             1044                                                                               i-C.sub.3 H.sub.7                                                                           H               CH.sub.2 C(CH.sub.3).sub.3                                                                 76                                1045                                                                               i-C.sub.3 H.sub.7                                                                           H               C.sub.6 H.sub.5                                                                           138-140                            1046                                                                               i-C.sub.3 H.sub.7                                                                           H               4-ClC.sub.6 H.sub.4                                                                       170-173                            1047                                                                               i-C.sub.3 H.sub. 7                                                                          H               3-CF.sub.3C.sub.6 H.sub.4                                                                 127                                1048                                                                               tert.-C.sub.4 H.sub.9                                                                       H               i-C.sub.3 H.sub.7                                                                          84-85                             1049                                                                               tert.-C.sub.4 H.sub.9                                                                       H               tert.-C.sub.4 H.sub.9                                                                     129-133                            1050                                                                               tert.-C.sub.4 H.sub.9                                                                       H               C.sub.6 H.sub.5                                                                           132-137                            1051                                                                               tert.-C.sub.4 H.sub.9                                                                       H               4-ClC.sub.6 H.sub.4                                                                       188-191                            1052                                                                               tert.-C.sub.4 H.sub.9                                                                       H               3-CF.sub.3C.sub.6 H.sub.4                                                                 160-162                            1053                                                                               cyclo-C.sub.6 H.sub.11                                                                      H               i-C.sub.3 H.sub.7                                                                         116-118                            1054                                                                               cyclo-C.sub.6 H.sub.11                                                                      H               tert.-C.sub.4 H.sub.9                                                                     158-159                            1055                                                                               cyclo-C.sub.6 H.sub.11                                                                      H               cyclo-C.sub.3 H.sub.5                                                                     142-143                            1056                                                                               cyclo-C.sub.6 H.sub.11                                                                      H               cyclo-C.sub.6 H.sub.11                        1057                                                                               cyclo-C.sub.6 H.sub.11                                                                      H               C.sub.6 H.sub.5                                                                           198-199                            1058                                                                               4-ClC.sub.6 H.sub.4                                                                         H               i-C.sub.3 H.sub.7                                                                         165-168                            1059                                                                               4-ClC.sub.6 H.sub.4                                                                         H               tert.-C.sub.4 H.sub.9                                                                     165-168                            1060                                                                               4-ClC.sub.6 H.sub.4                                                                         H               C.sub.6 H.sub.5                                                                           220                                1061                                                                               4-ClC.sub.6 H.sub.4                                                                         H               4-ClC.sub.6 H.sub.4                           1062                                                                               4-ClC.sub.6 H.sub.4                                                                         H               3-CF.sub.3C.sub.6 H.sub.4                                                                 209-211                            1063                                                                               i-C.sub.3 H.sub. 7                                                                          succinimido     cyclo-C.sub.3 H.sub.5                                                                     108-109                            1064                                                                               CH.sub.3     H               C(CH.sub.3).sub.2 CCH                                                                      80-87                             1065                                                                               CH.sub.3     C.sub.2 H.sub.5 C(CH.sub.3).sub.2 CCH                                                                      82-86                             1066                                                                               CH.sub.3     Na.sup.⊕    tert.-C.sub.4 H.sub.9                                                                     220                                1067                                                                               CH.sub.3     K.sup.⊕     tert.-C.sub.4 H.sub.9                                                                     288                                1068                                                                               CH.sub.3     H.sub.3 N.sup.⊕ CH(CH.sub.3).sub.2                                                         tert.-C.sub.4 H.sub.9                                                                     184-187                            1069                                                                               CH.sub.3     H.sub.3 N.sup.⊕CH.sub.2 CH.sub.2 OH                                                        tert.-C.sub.4 H.sub.9                                                                     124-126                            1070                                                                               C.sub.2 H.sub.5                                                                             Na.sup.⊕    tert.-C.sub.4 H.sub.9                                                                     150                                1071                                                                               C.sub.2 H.sub.5                                                                             K.sup.⊕     tert.-C.sub.4 H.sub.9                                                                     220                                1072                                                                               C.sub.2 H.sub.5                                                                             H.sub.3 N.sup.⊕CH(CH.sub.3).sub.2                                                          tert.-C.sub.4 H.sub.9                                                                     170-172                            1073                                                                               C.sub.2 H.sub.5                                                                             H.sub.3 N.sup.⊕CH.sub.2 CH.sub.2 OH                                                        tert.-C.sub.4 H.sub.9                                                                     105-108                            1074                                                                               C.sub.2 H.sub.5                                                                             succinimido     tert.-C.sub.4 H.sub.9                                                                     163-165                            1075                                                                               C.sub.2 H.sub.5                                                                             N C(CH.sub.3).sub.2                                                                            tert.-C.sub.4 H.sub.9                                                                      68-70                             1076                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2 CCH    tert.-C.sub.4 H.sub.9                                                                     oil 1.35(t; 3H),                                                               1.48(s; 9H),                                                                   2.63(t; 1H),                                                                   2.96; 4.98                                                                     (d; 2H),                                                                       8.95(bs;                                                                       1H, NH)                            1077                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5                                                             tert.-C.sub.4 H.sub.9                                                                      74-76                             1078                                                                               cyclo-C.sub.3 H.sub.5                                                                       H               i-C.sub.3 H.sub.7                                                                          78-80                             1079                                                                               cyclo-C.sub.3 H.sub.5                                                                       H               tert.-C.sub.4 H.sub.9                                                                      87-88                             1080                                                                               cyclo-C.sub.3 H.sub.5                                                                       H               C.sub.6 H.sub.5                                                                           162-163                            1081                                                                               cyclo-C.sub.6 H.sub.11                                                                      succinimido     i-C.sub.3 H.sub.7                                                                         126-127                            1082                                                                               cyclo-C.sub.6 H.sub.11                                                                      succinimido     tert.-C.sub.4 H.sub.9                                                                     172-174                            1083                                                                               cyclo-C.sub.6 H.sub.11                                                                      succinimido     C.sub.6 H.sub.5                                                                           176-177                            1084                                                                               tetrahydro-pyran-3-yl                                                                       H               i-C.sub.3 H.sub.7                                                                         157-160                            1085                                                                               tetrahydro-pyran-3-yl                                                                       H               tert.-C.sub.4 H.sub.9                                                                      91-95                             1086                                                                               tetrahydro-pyran-3-yl                                                                       H               cyclo-C.sub.3 H.sub.5                                                                     158-160                            1087                                                                               tetrahydro-pyran-3-yl                                                                       H               C.sub.6 H.sub.5                                                                           152-157                            1088                                                                               CH.sub.3     pyrid-3-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1089                                                                               CH.sub.3     thien-2-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1090                                                                               CH.sub.3     CH.sub.2CH.sub.2N(CH.sub.3).sub.2                                                              tert.-C.sub.4 H.sub.9                         1091                                                                               CH.sub.3                                                                                     ##STR24##      tert.-C.sub.4 H.sub.9                         1092                                                                               CH.sub.3     CH.sub.2CF.sub.3                                                                               tert.-C.sub.4 H.sub.9                         1093                                                                               CH.sub.3     CH.sub.2C(CH.sub.3)CH.sub.2                                                                    tert.-C.sub.4 H.sub.9                         1094                                                                               CH.sub.3     CH.sub.2 C(Cl)CH.sub.2                                                                         tert.-C.sub.4 H.sub.9                         1095                                                                               CH.sub.3     CH.sub.2CCCH.sub.2 OH                                                                          tert.-C.sub.4 H.sub.9                         1096                                                                               CH.sub.3                                                                                     ##STR25##      tert.-C.sub.4 H.sub.9                         1097                                                                               CH.sub.3                                                                                     ##STR26##      tert.-C.sub.4 H.sub.9                         1098                                                                               CH.sub.3                                                                                     ##STR27##      tert.-C.sub.4 H.sub.9                         1099                                                                               CH.sub.3     phenethyl       tert.-C.sub.4 H.sub.9                         1100                                                                               CH.sub.3     CH(C.sub.6 H.sub.5)COOCH.sub.3                                                                 tert.-C.sub.4 H.sub.9                         1101                                                                               CH.sub.3     cyclo-C.sub.6 H.sub.11                                                                         tert.-C.sub.4 H.sub.9                         1102                                                                               CH.sub.3     CH.sub.2OCH.sub.2C.sub.6 H.sub.5                                                               tert.-C.sub.4 H.sub.9                         1103                                                                               CH.sub.3     tetrahydro-pyran-2-yl                                                                          tert.-C.sub.4 H.sub.9                         1104                                                                               CH.sub.3     tetrahydro-fur-2-yl                                                                            tert.-C.sub.4 H.sub.9                         1105                                                                               CH.sub.3     (4-bromobenzoyl)-methyl                                                                        tert.-C.sub.4 H.sub.9                         1106                                                                               CH.sub.3     (4-methoxybenzoyl)methyl                                                                       tert.-C.sub.4 H.sub.9                         1107                                                                               CH.sub.3     CH(COOCH.sub.3).sub.2                                                                          tert.-C.sub.4 H.sub.9                         1108                                                                               CH.sub.3     phthalimidomethyl                                                                              tert.-C.sub.4 H.sub.9                         1109                                                                               CH.sub.3     CH.sub.2CH.sub.2Si(CH.sub.3).sub.3                                                             tert.-C.sub.4 H.sub.9                         1110                                                                               CH.sub.3     CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2                                                            tert.-C.sub.4 H.sub.9                         1111                                                                               CH.sub.3     CH.sub.2PO(OC.sub.2 H.sub.5).sub.2                                                             tert.-C.sub.4 H.sub.9                         1112                                                                               CH.sub.3     fur-2-yl-methyl tert.-C.sub.4 H.sub.9                         1113                                                                               CH.sub.3     tetrahydrofur-2-yl-methyl                                                                      tert.-C.sub.4 H.sub.9                         1114                                                                               CH.sub.3     pyrid-2-ylmethyl                                                                               tert.-C.sub.4 H.sub.9                         1115                                                                               CH.sub.3     pyrid-4-ylmethyl                                                                               tert.-C.sub.4 H.sub.9                         1116                                                                               CH.sub.3     piperidino      tert.-C.sub.4 H.sub.9                         1117                                                                               CH.sub.3     phthalimido     tert.-C.sub.4 H.sub.9                         1118                                                                               CH.sub.3                                                                                     ##STR28##      tert.-C.sub.4 H.sub.9                         1119                                                                               CH.sub.3     NCHC.sub.6 H.sub.5                                                                             tert.-C.sub.4 H.sub.9                         1120                                                                               CH.sub.3                                                                                     ##STR29##      tert.-C.sub.4 H.sub.9                         1121                                                                               CH.sub.3     CH(CH.sub.3)CH(OCH.sub.3).sub.2                                                                tert.-C.sub.4 H.sub.9                         1122                                                                               CH.sub.3     CH.sub.2CON(C.sub.2 H.sub.5).sub.2                                                             tert.-C.sub.4 H.sub.9                         1123                                                                               CH.sub.3     N(C.sub.2 H.sub.5).sub.2                                                                       tert.-C.sub.4 H.sub.9                         1124                                                                               C.sub.2 H.sub.5                                                                             cyclo-C.sub.6 H.sub.11                                                                         tert.-C.sub.4 H.sub.9                         1125                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2OCH.sub.2C.sub.6 H.sub.5                                                               tert.-C.sub.4 H.sub.9                         1126                                                                               C.sub.2 H.sub.5                                                                             tetrahydro-pyran-2-yl                                                                          tert.-C.sub.4 H.sub.9                         1127                                                                               C.sub.2 H.sub.5                                                                             tetrahydro-fur-2-yl                                                                            tert.-C.sub.4 H.sub.9                         1128                                                                               C.sub.2 H.sub.5                                                                             (4-bromobenzoyl)-methyl                                                                        tert.-C.sub.4 H.sub.9                         1129                                                                               C.sub.2 H.sub.5                                                                             (4-methoxybenzoyl)-methyl                                                                      tert.-C.sub.4 H.sub.9                         1130                                                                               C.sub.2 H.sub.5                                                                             CH(COOCH.sub.3).sub.2                                                                          tert.-C.sub.4 H.sub.9                         1131                                                                               C.sub.2 H.sub.5                                                                             phthalimidomethyl                                                                              tert.-C.sub.4 H.sub.9                         1132                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2CH.sub.2Si(CH.sub.3).sub.3                                                             tert.-C.sub.4 H.sub.9                         1133                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2                                                            tert.-C.sub.4 H.sub.9                         1134                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2PO(OC.sub.2 H.sub.5).sub.2                                                             tert.-C.sub.4 H.sub.9                         1135                                                                               C.sub.2 H.sub.5                                                                             fur-2-ylmethyl  tert.-C.sub.4 H.sub.9                         1136                                                                               C.sub.2 H.sub.5                                                                             tetrahydrofur-2-yl-methyl                                                                      tert.-C.sub.4 H.sub.9                         1137                                                                               C.sub.2 H.sub.5                                                                             pyrid-2-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1138                                                                               C.sub.2 H.sub.5                                                                             pyrid-4-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1139                                                                               C.sub.2 H.sub.5                                                                             pyrid-3-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1140                                                                               C.sub.2 H.sub.5                                                                             thien-2-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1141                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2CH.sub.2N(CH.sub.3).sub.2                                                              tert.-C.sub.4 H.sub.9                         1142                                                                               C.sub.2 H.sub.5                                                                              ##STR30##      tert.-C.sub.4 H.sub.9                         1143                                                                               C.sub.2 H.sub.5                                                                             CH.sub. 2CF.sub.3                                                                              tert.-C.sub.4 H.sub.9                         1144                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2C(CH.sub.3)CH.sub.2                                                                    tert.-C.sub.4 H.sub.9                         1145                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2 C(Cl)CH.sub.2                                                                         tert.-C.sub.4 H.sub.9                         1146                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2CCCH.sub.2 OH                                                                          tert.-C.sub.4 H.sub.9                         1147                                                                               C.sub.2 H.sub.5                                                                              ##STR31##      tert.-C.sub.4 H.sub.9                         1148                                                                               C.sub.2 H.sub.5                                                                              ##STR32##      tert.-C.sub.4 H.sub.9                         1149                                                                               C.sub.2 H.sub.5                                                                              ##STR33##      tert.-C.sub.4 H.sub.9                         1150                                                                               C.sub.2 H.sub.5                                                                             phenethyl       tert.-C.sub.4 H.sub.9                         1151                                                                               C.sub.2 H.sub.5                                                                             CH(C.sub.6 H.sub.5)COOCH.sub.3                                                                 tert.-C.sub.4 H.sub.9                         1152                                                                               C.sub.2 H.sub.5                                                                             piperidino      tert.-C.sub.4 H.sub.9                         1153                                                                               C.sub.2 H.sub.5                                                                             phthalimido     tert.-C.sub.4 H.sub.9                         1154                                                                               C.sub.2 H.sub.5                                                                              ##STR34##      tert.-C.sub.4 H.sub.9                         1155                                                                               C.sub.2 H.sub.5                                                                             NCHC.sub.6 H.sub.5                                                                             tert.-C.sub.4 H.sub.9                         1156                                                                               C.sub.2 H.sub.5                                                                              ##STR35##      tert.-C.sub.4 H.sub.9                         1157                                                                               C.sub.2 H.sub.5                                                                             CH(CH.sub.3)CH(OCH.sub.3).sub.2                                                                tert.-C.sub.4 H.sub.9                         1158                                                                               C.sub.2 H.sub.5                                                                             CH.sub.2CON(C.sub.2 H.sub.5).sub.2                                                             tert.-C.sub.4 H.sub.9                         1159                                                                               C.sub.2 H.sub.5                                                                             N(C.sub.2 H.sub.5).sub.2                                                                       tert.-C.sub.4 H.sub.9                         1160                                                                               i-C.sub.3 H.sub.7                                                                           cyclo-C.sub.6 H.sub.11                                                                         tert.-C.sub.4 H.sub.9                         1161                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2OCH.sub.2C.sub.6 H.sub.5                                                               tert.-C.sub.4 H.sub.9                         1162                                                                               i-C.sub.3 H.sub.7                                                                           tetrahydro-pyran-2-yl                                                                          tert.-C.sub.4 H.sub.9                         1163                                                                               i-C.sub.3 H.sub.7                                                                           tetrahydro-fur-2-yl                                                                            tert.-C.sub.4 H.sub.9                         1164                                                                               i-C.sub.3 H.sub.7                                                                           (4-bromobenzoyl)-methyl                                                                        tert.-C.sub.4 H.sub.9                         1165                                                                               i-C.sub.3 H.sub.7                                                                           (4-methoxybenzoyl)methyl                                                                       tert.-C.sub.4 H.sub.9                         1166                                                                               i-C.sub.3 H.sub.7                                                                           CH(COOCH.sub.3).sub.2                                                                          tert.-C.sub.4 H.sub.9                         1167                                                                               i-C.sub.3 H.sub.7                                                                           phthalimidomethyl                                                                              tert.-C.sub.4 H.sub.9                         1168                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CH.sub.2Si(CH.sub.3).sub.3                                                             tert.-C.sub.4 H.sub.9                                                                      64-69                             1169                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2                                                            tert.-C.sub.4 H.sub.9                         1170                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2PO(OC.sub.2 H.sub.5).sub.2                                                             tert.-C.sub.4 H.sub.9                         1171                                                                               i-C.sub.3 H.sub.7                                                                           fur-2-ylmethyl  tert.-C.sub.4 H.sub.9                         1172                                                                               i-C.sub.3 H.sub.7                                                                           tetrahydrofur-2-yl-methyl                                                                      tert.-C.sub.4 H.sub.9                         1173                                                                               i-C.sub.3 H.sub.7                                                                           pyrid-2-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                                                                     oil; 1.30(s; 6H)                                                               1.44 (s; 9H),                                                                  3.40 (sept; 1H)                                                                5.52 (s; 2H)                                                                   7.20-8.64                                                                      (m; 4H), 8.60                                                                  (bs; 1H, NH)                       1174                                                                               i-C.sub.3 H.sub.7                                                                           pyrid-4-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1175                                                                               i-C.sub.3 H.sub.7                                                                           pyrid-3-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1176                                                                               i-C.sub.3 H.sub.7                                                                           thien-2-yl-methyl                                                                              tert.-C.sub.4 H.sub.9                         1177                                                                               i-C.sub.3 H.sub.7                                                                            CH.sub.2CH.sub.2N(CH.sub.3).sub.2                                                             tert.-C.sub.4 H.sub.9                         1178                                                                               i-C.sub.3 H.sub.7                                                                            ##STR36##      tert.-C.sub.4 H.sub.9                         1179                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CF.sub.3                                                                               tert.-C.sub.4 H.sub.9                         1352                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2C(CH.sub.3)CH.sub.2                                                                    tert.-C.sub.4 H.sub.9                         1153                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2 C(Cl)CH.sub.2                                                                         tert.-C.sub.4 H.sub.9                         1154                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CCCH.sub.2 OH                                                                          tert.-C.sub.4 H.sub.9                         1155                                                                               i-C.sub.3 H.sub.7                                                                            ##STR37##      tert.-C.sub.4 H.sub.9                         1156                                                                               i-C.sub.3 H.sub.7                                                                            ##STR38##      tert.-C.sub.4 H.sub.9                         1157                                                                               i-C.sub.3 H.sub.7                                                                            ##STR39##      tert.-C.sub.4 H.sub.9                         1180                                                                               i-C.sub.3 H.sub.7                                                                           phenethyl       tert.-C.sub.4 H.sub.9                         1181                                                                               i-C.sub.3 H.sub.7                                                                           CH(C.sub.6 H.sub.5)COOCH.sub.3                                                                 tert.-C.sub.4 H.sub.9                         1182                                                                               i-C.sub.3 H.sub.7                                                                           piperidino      tert.-C.sub.4 H.sub.9                         1183                                                                               i-C.sub.3 H.sub.7                                                                           phthalimido     tert.-C.sub.4 H.sub.9                         1184                                                                               i-C.sub.3 H.sub.7                                                                            ##STR40##      tert.-C.sub.4 H.sub.9                         1185                                                                               i-C.sub.3 H.sub.7                                                                           NCHC.sub.6 H.sub.5                                                                             tert.-C.sub.4 H.sub.9                         1186                                                                               i-C.sub.3 H.sub.7                                                                            ##STR41##      tert.-C.sub.4 H.sub.9                         1187                                                                               i-C.sub.3 H.sub.7                                                                           CH(CH.sub.3 CH)(OCH.sub.3).sub.2                                                               tert.-C.sub.4 H.sub.9                         1188                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CON(C.sub.2 H.sub.5).sub.2                                                             tert.-C.sub.4 H.sub.9                                                                      91-93                             1189                                                                               i-C.sub.3 H.sub.7                                                                           N(C.sub.2 H.sub.5).sub.2                                                                       tert.-C.sub.4 H.sub.9                         1190                                                                               CH.sub.3     NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                     108-109                            1191                                                                               CH.sub.3     cyclohexanimino tert.-C.sub.4 H.sub.9                                                                      91-92                             1192                                                                               CH.sub.3     NC(cyclo-C.sub.3 H.sub.5).sub.2                                                                tert.-C.sub.4 H.sub.9                                                                      50-52                             1193                                                                               CH.sub.3     H               N(CH.sub.3).sub.2                                                                         225-227                            1194                                                                               CH.sub.3     H               piperidino 162-164                            1195                                                                               CH.sub.3     CH.sub.2CCH     tert.-C.sub.4 H.sub.9                                                                      90-95                             1197                                                                               CH.sub.3     2-NO.sub.2 -4-FC.sub.6 H.sub.3                                                                 tert.-C.sub.4 H.sub.9                                                                     oil; 1.44(s; 9H),                                                              2.59(s; 3H),                                                                   7.24 and 8.30                                                                  (m; 3H), 8.16                                                                  (bs; 1H, NH)                       1198                                                                               CH.sub.3     3,5-(CF.sub.3).sub.2C.sub.6 H.sub.3                                                            tert.-C.sub.4 H.sub.9                                                                     156-159                            1199                                                                               CH.sub.3     H               CH.sub.3   192-197                            1200                                                                               CH.sub.3     H               OC.sub.2 H.sub.5                                                                          145-148                            1201                                                                               CH.sub.3     H               cyclo-C.sub.4 H.sub.7                                                                     141-142                            1202                                                                               CH.sub.3     H               cyclo-C.sub.3 H.sub.5                                                                     135-137                            1203                                                                               CH.sub.3     NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                      91-93                             1204                                                                               CH.sub.3     H               C.sub.2 H.sub.5                                                                           151-154                            1205                                                                               CH.sub.3     NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.4 H.sub.7                                                                      77-79                             1207                                                                               CH.sub.3     CH.sub.2 CO.sub.2 CH.sub.3                                                                     tert.-C.sub.4 H.sub.9                                                                      88-89                             1208                                                                               C.sub.2 H.sub.5                                                                             succinimido     i-C.sub.3 H.sub.7                                                                         132-136                            1209                                                                               n-C.sub.3 H.sub.7                                                                           H               cyclo-C.sub.6 H.sub.11                                                                    132-134                            1210                                                                               n-C.sub.3 H.sub.7                                                                           H               tert.-C.sub.4 H.sub.9                                                                      82-83                             1211                                                                               n-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                      66-68                             1212                                                                               n-C.sub.3 H.sub.7                                                                           succinimido     tert.-C.sub.4 H.sub.9                                                                     126-129                            1213                                                                               n-C.sub.3 H.sub.7                                                                           succinimido     cyclo-C.sub.3 H.sub.5                                                                     104-106                            1214                                                                               n-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                     oil 0.70(m; 2H),                                                               0.90(m; 2H),                                                                   1.00(t; 3H),                                                                   1.78(m; 2H),                                                                   2.16 and 2.19                                                                  (2s; 6H), 2.92                                                                 (t; 2H), 3.00                                                                  (m; 1H), 9.24                                                                  (bs; 1H, NH)                       1215                                                                               n-C.sub.3 H.sub.7                                                                           H               cyclo-C.sub.3 H.sub.5                                                                     104-106                            1216                                                                               n-C.sub.3 H.sub.7                                                                           H               i-C.sub.3 H.sub.7                                                                          70-71                             1217                                                                               n-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             i-C.sub.3 H.sub.7                                                                          72-73                             1218                                                                               n-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.6 H.sub.11                                                                    110-111                            1219                                                                               n-C.sub.3 H.sub.7                                                                           H               C.sub.6 H.sub.5                                                                           165-166                            1220                                                                               i-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                     112-113                            1221                                                                               i-C.sub.3 H.sub.7                                                                            ##STR42##      tert.-C.sub.4 H.sub.9                                                                      83-86                             1222                                                                               i-C.sub.3 H.sub.7                                                                           cyclohexanimino tert.-C.sub.4 H.sub.9                                                                      91-94                             1223                                                                               i-C.sub.3 H.sub.7                                                                           NC(cyclo-C.sub.3 H.sub.5).sub.2                                                                tert.-C.sub.4 H.sub.9                                                                      70-75                             1224                                                                               i-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             tetrahydrofur-3-yl                                                                        104-106                            1225                                                                               i-C.sub.3 H.sub.7                                                                           succinimido     tetrahydrofur-3-yl                                                                        160-162                            1226                                                                               i-C.sub.3 H.sub.7                                                                           H               tetrahydrofur-3-yl                                                                        oil 1.33(d; 6H),                                                               2.40(m; 2H),                                                                   3.75(sept; 1H),                                                                4.00(m; 4H),                                                                   4.75 (m; 1H),                                                                  8.25 (d; 1H,NH)                    1227                                                                               i-C.sub.3 H.sub. 7                                                                          H               OC.sub.2 H.sub.5                                                                          134-135                            1228                                                                               i-C.sub.3 H.sub.7                                                                           succinimido     OC.sub.2 H.sub.5                                                                          146-148                            1229                                                                               i-C.sub.3 H.sub.7                                                                           H               thiazol-2-yl                                                                              195                                1230                                                                               i-C.sub.3 H.sub.7                                                                           H               5-methyl-thiazol-                                                                         248                                                                 2-yl                                          1231                                                                               i-C.sub.3 H.sub.7                                                                           H               5-ethyl-thiazol-                                                                          228-230                                                             2-yl                                          1232                                                                               i-C.sub.3 H.sub.7                                                                           H               5-n-propyl-thiazol-                                                                       160-163                                                             2-yl                                          1233                                                                               i-C.sub.3 H.sub.7                                                                           succinimido     tert.-C.sub.4 H.sub.9                                                                     141-144                            1234                                                                               i-C.sub.3 H.sub.7                                                                           H               cyclo-C.sub.4 H.sub.7                                                                      95-96                             1235                                                                               i-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.4 H.sub.7                                                                     100-101                            1236                                                                               i-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             N(CH.sub.3).sub.2                                                                         129-131                            1237                                                                               i-C.sub.3 H.sub.7                                                                           H               N(CH.sub.3).sub.2                                                                         163-165                            1238                                                                               i-C.sub.3 H.sub.7                                                                           H               piperidino 167-168                            1239                                                                               i-C.sub.3 H.sub.7                                                                           H               morpholino 177-179                            1240                                                                               i-C.sub.3 H.sub.7                                                                           H               cyclo-C.sub.5 H.sub.9                                                                      62-65                             1241                                                                               i-C.sub.3 H.sub.7                                                                           H               cyclopropylmethyl                                                                          88-90                             1242                                                                               i-C.sub.3 H.sub.7                                                                           H               s-C.sub.4 H.sub.9                                                                         oil; 1.00(t; 3H),                                                              1.34(d; 3H),                                                                   1.37(d; 6H),                                                                   1.66(quint; 2H),                                                               3.78 (sept; 1H),                                                               4.17(m; 1H),                                                                   7.04 (d, 1H, NH)                   1243                                                                               i-C.sub.3 H.sub.7                                                                           NC(CH.sub.3).sub.2                                                                             s-C.sub.4 H.sub.9                                                                         oil; 0.98(t; 3H),                                                              1.26(d, 3H),                                                                   1, 39 (d, 6H)                                                                  1.64 (quint;                                                                   2H), 2.16 and                                                                  2.18 (2s; 6H)                                                                  3.44 (sept; 1H),                                                               4.10 (m, 1H),                                                                  8.54 (d, 1H, NH)                   1244                                                                               i-C.sub.3 H.sub.7                                                                           H               mixture of 197                                                                 4-methyl-5-carboxy-                                                            thiazol-2-yl and                                                               4-methyl-thiazol-2-yl                         1245                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CHCHC.sub.6 H.sub.5                                                                    tert.-C.sub.4 H.sub.9                                                                      59-63                             1246                                                                               i-C.sub.3 H.sub.7                                                                           4-CO.sub.2 CH.sub.3 C.sub.6 H.sub.4                                                            tert.-C.sub.4 H.sub.9                                                                     143-145                            1247                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CH.sub.2CN                                                                             tert.-C.sub.4 H.sub.9                                                                      67-71                             1248                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CCl.sub.3                                                                              tert.-C.sub.4 H.sub.9                                                                      72-75                             1249                                                                               i-C.sub.3 H.sub.7                                                                           4-NHCOCH.sub.3C.sub.6 H.sub.4                                                                  tert.-C.sub.4 H.sub.9                                                                     212-214                            1250                                                                               i-C.sub.3 H.sub.7                                                                           2,4-Cl.sub.2C.sub.6 H.sub.3                                                                    tert.-C.sub.4 H.sub.9                                                                     140-141                            1251                                                                               i-C.sub.3 H.sub.7                                                                           cyclooctanimino tert.-C.sub.4 H.sub.9                                                                     oil, 1.37(d, 6H),                                                              1.47(s; 9H),                                                                   1.28-1.93                                                                      (m; 10H), 2.54                                                                 (m; 4H), 3.44                                                                  (sept, 1H), 8.44                                                               (bs; 1H, NH)                       1252                                                                               i-C.sub.3 H.sub.7                                                                           (CH.sub.2).sub.2 O(CH.sub.2).sub.2 OCH.sub.3                                                   tert.-C.sub.4 H.sub.9                                                                     oil, 1.34(d; 6H),                                                              1.47 (s; 9H),                                                                  3.39 (s; 3H),                                                                  3.45 (sept; 1H),                                                               3.60 (m; 4H),                                                                  3.84 and 4.50                                                                  (m; 4H), 8.94                                                                  (bs; 1H, NH)                       1253                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CH.sub.2SCH.sub.3                                                                      tert.-C.sub.4 H.sub.9                                                                      46-48                             1254                                                                               i-C.sub.3 H.sub.7                                                                           Pyrid-2-yl      tert.-C.sub.4 H.sub.9                                                                     155-163                            1255                                                                               i-C.sub.3 H.sub.7                                                                           CH.sub.2CH.sub.2Cl                                                                             tert.-C.sub. 4 H.sub.9                                                                     70-72                             1263                                                                               n-C.sub.4 H.sub.9                                                                           H               CH.sub.3   146-149                            1264                                                                               n-C.sub.4 H.sub.9                                                                           H               i-C.sub.3 H.sub.7                                                                          60-63                             1265                                                                               n-C.sub.4 H.sub.9                                                                           H               cyclo-C.sub.3 H.sub.5                                                                     112-114                            1266                                                                               n-C.sub.4 H.sub.9                                                                           H               C.sub.6 H.sub.5                                                                           145-150                            1267                                                                               n-C.sub.4 H.sub.9                                                                           H               tert.-C.sub.4 H.sub.9                                                                      52-54                             1268                                                                               n-C.sub.4 H.sub.9                                                                           NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                      58-62                             1269                                                                               n-C.sub.4 H.sub.9                                                                           CH.sub.2 CCl.sub.3                                                                             tert.-C.sub.4 H.sub.9                                                                     oil 0.92 (t; 3H),                                                              1.43 (m, 2H),                                                                  1.48(s; 9H),                                                                   1.74(m; 2H)                                                                    3.00(t; 2H),                                                                   5.01(s; 2H),                                                                   8.80(bs; 1H; NH)                   1270                                                                               n-C.sub.4 H.sub.9                                                                           2,6-Br.sub.2 -4-CNC.sub.6 H.sub.2                                                              tert.-C.sub.4 H.sub.9                                                                     165-170                            1271                                                                               n-C.sub.4 H.sub.9                                                                           CH.sub.2CHCH.sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                     oil 0.92(t; 3H),                                                               1.41(m; 2H),                                                                   1.46(s; 9H),                                                                   1.66(m; 2H),                                                                   2.89(t; 2H),                                                                   4.88(d; 2H),                                                                   5.40(m; 2H),                                                                   6.01(m; 1H),                                                                   9.19(bs; 1H, NH)                   1272                                                                               n-C.sub.4 H.sub.9                                                                           2,4-dichlorobenzyl                                                                             tert.-C.sub.4 H.sub.9                                                                      81-86                             1273                                                                               n-C.sub.4 H.sub.9                                                                           H               cyclopropylmethyl                                                                          65-70                             1274                                                                               s-C.sub.4 H.sub.9                                                                           H               i-C.sub.3 H.sub.7                                                                         oil 0.92 (t, 3H),                                                              1.34(d, 3H),                                                                   1.39(d; 6H),                                                                   1.76(m; 2H),                                                                   3.65(m; 1H),                                                                   4.32(m; 1H),                                                                   7.08(bs; 1H, NH)                   1275                                                                               s-C.sub.4 H.sub.9                                                                           NC(CH.sub.3).sub.2                                                                             i-C.sub.3 H.sub.7                                                                          80-84                             1276                                                                               s-C.sub.4 H.sub.9                                                                           H               cyclo-C.sub.3 H.sub.7                                                                      78-85                             1277                                                                               s-C.sub.4 H.sub.9                                                                           NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                     oil 0.70(m,; 2H),                                                              0.90 (m; 2H),                                                                  0.92 (t; 3H),                                                                  1.34 (d; 3H),                                                                  1.79 (m; 2H),                                                                  2.14 and 2.18                                                                  (2s; 6H), 2.97                                                                 (m; 1H), 3.24                                                                  (m; 1H), 8.80                                                                  (bs, 1H, NH)                       1278                                                                               s-C.sub.4 H.sub.9                                                                           succinimido     cyclo-C.sub.3 H.sub.5                                                                     112-115                            1279                                                                               s-C.sub.4 H.sub.9                                                                           H               tert.-C.sub.4 H.sub.9                                                                      93-95                             1280                                                                               s-C.sub.4 H.sub.9                                                                           NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                     oil 0.92 (t, 3H),                                                              1.34 (d; 3H),                                                                  1.48 (s; 9H),                                                                  1.80 (m; 2H),                                                                  2.12 and 2.16                                                                  (2s; 6H), 3.26                                                                 (m, 1H), 8.29                                                                  (bs, 1H, NH)                       1281                                                                               s-C.sub.4 H.sub.9                                                                           H               C.sub.6 H.sub.5                                                                           117-120                            1282                                                                               s-C.sub.4 H.sub.9                                                                           NC(CH.sub.3).sub.2                                                                             C.sub.6 H.sub.5                                                                           oil, 0.93(t; 3H),                                                              1.36 (d; 3H),                                                                  1.80 (m; 2H),                                                                  2.14 and 2.18                                                                  (2s; 6H), 3.28                                                                 (m; 1H),                                                                       7.10-7.80(m; 5H)                                                               10.90(bs; 1H), NH)                 1283                                                                               tert.-C.sub.4 H.sub.9                                                                       succinimido     i-C.sub.3 H.sub.7                                                                         137-140                            1284                                                                               tert.-C.sub.4 H.sub.9                                                                       succinimido     4-ClC.sub.6 H.sub.4                                                                       238-242                            1285                                                                               tert.-C.sub.4 H.sub.9                                                                       succinimido     tert.-C.sub.4 H.sub.9                                                                     144-146                            1286                                                                               tert.-C.sub.4 H.sub.9                                                                       NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                      86-90                             1287                                                                               tert.-C.sub.4 H.sub.9                                                                       H               cyclo-C.sub.3 H.sub.5                                                                      75-77                             1288                                                                               tert.-C.sub.4 H.sub.9                                                                       NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                      93-98                             1290                                                                               neo-C.sub.5 H.sub.11                                                                        H               CH.sub.3   130-133                            1291                                                                               neo-C.sub.5 H.sub.11                                                                        H               i-C.sub.3 H.sub.7                                                                         100-104                            1292                                                                               neo-C.sub.5 H.sub.11                                                                        H               cyclo-C.sub.3 H.sub.5                                                                     133-136                            1293                                                                               neo-C.sub.5 H.sub.11                                                                        NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                      56-62                             1294                                                                               neo-C.sub.5 H.sub.11                                                                        H               tert.-C.sub.4 H.sub.9                                                                     112-117                            1295                                                                               neo-C.sub.5 H.sub.11                                                                        NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                     107-111                            1296                                                                               neo-C.sub.5 H.sub.11                                                                        H               C.sub.6 H.sub.5                                                                           205-207                            1297                                                                               cyclo-C.sub.3 H.sub.5                                                                       succinimido     i-C.sub.3 H.sub.7                                                                         131-133                            1298                                                                               cyclo-C.sub.3 H.sub.5                                                                       succinimido     tert.-C.sub.4 H.sub.9                                                                     167-168                            1299                                                                               cyclo-C.sub.3 H.sub.5                                                                       succinimido     C.sub.6 H.sub.5                                                                           168-170                            1300                                                                               cyclo-C.sub.3 H.sub.5                                                                       H               cyclo-C.sub.3 H.sub.5                                                                     139-140                            1301                                                                               cyclo-C.sub.3 H.sub.5                                                                       NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                     oil 0.80 (m; 8H),                                                              2.02 and 2.04                                                                  (2s; 6H), 2.30                                                                 (m; 1H), 2.86                                                                  (m; 1H), 9.20                                                                  (d; 1H, NH)                        1302                                                                               cyclo-C.sub.3 H.sub.5                                                                       NC(cyclo-C.sub.3 H.sub.5).sub.2                                                                cyclo-C.sub.3 H.sub.7                                                                     106-108                            1303                                                                               cyclo-C.sub.3 H.sub.5                                                                       H               cyclo-C.sub.5 H.sub.9                                                                     106-109                            1304                                                                               cyclo-C.sub.3 H.sub.5                                                                       NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.5 H.sub.9                                                                     125-127                            1305                                                                               cyclo-C.sub.5 H.sub.9                                                                       H               C.sub.6 H.sub.5                                                                           170-171                            1306                                                                               cyclo-C.sub.5 H.sub.9                                                                       H               cyclo-C.sub.3 H.sub.5                                                                     118-120                            1307                                                                               cyclo-C.sub.5 H.sub.9                                                                       NC(CH.sub.3).sub.2                                                                             cyclo-C.sub.3 H.sub.5                                                                      55-57                             1308                                                                               cyclo-C.sub.5 H.sub.9                                                                       NC(CH.sub.3).sub.2                                                                             CH.sub.3   100-101                            1309                                                                               cyclo-C.sub.5 H.sub.9                                                                       H               CH.sub.3   166-167                            1310                                                                               cyclo-C.sub.5 H.sub.9                                                                       H               tert.-C.sub.4 H.sub.9                                                                     125-126                            1311                                                                               cyclo-C.sub.5 H.sub.9                                                                       NC(CH.sub.3).sub. 2                                                                            tert.-C.sub.4 H.sub.9                                                                     112-114                            1312                                                                               tetrahydro-pyran-3-yl                                                                       succinimido     C.sub.6 H.sub.5                                                                            80                                1313                                                                               2-CH.sub.3 OC.sub.6 H.sub.4                                                                 H               tert.-C.sub.4 H.sub.9                                                                     179-184                            1314                                                                               2-CH.sub.3 OC.sub.6 H.sub.4                                                                 H               cyclo-C.sub.4 H.sub.5                                                                     177-180                            1315                                                                               2,6F.sub.2C.sub.6 H.sub.3                                                                   H               tert.-C.sub.4 H.sub.9                                                                     128-135                            1316                                                                               2,6F.sub.2C.sub.6 H.sub.3                                                                   H               cyclo-C.sub.3 H.sub.5                                                                     134-138                            1317                                                                               CH.sub.3O    H               tert.-C.sub.4 H.sub.9                                                                     oil 1.52 (s; 9H),                                                              4.12(s; 3H),                                                                   7.16(bs; 1H, NH)                   1318                                                                               CH.sub.3OCH.sub.2                                                                           H               tert.-C.sub.4 H.sub.9                                                                      95-100                            1319                                                                               CH.sub.3OCH.sub.2                                                                           H               cyclo-C.sub.3 H.sub.5                                                                      90-95                             1320                                                                               CH.sub.3OCH.sub.2                                                                           NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                      65-70                             1321                                                                               CH.sub.3OCH(CH.sub.3)                                                                       NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                     oil 1.45 (s; 9H)                                                               1.60 (d; 3H),                                                                  2.16 and 2.18                                                                  (2s; 6H), 3.34                                                                 (s; 3H), 4.87                                                                  (quart.; 1H)                                                                   8.10(bs; 1H, NH)                   1322                                                                               CH.sub.3OCH(CH.sub.3)                                                                       H               tert.-C.sub.4 H.sub.9                                                                      69-71                             1323                                                                               CH.sub.3OCH(CH.sub.3)                                                                       2,6-Br.sub.2 4-CNC.sub.6 H.sub.2                                                               tert.-C.sub.4 H.sub.9                                                                     118-120                            1324                                                                               CH.sub.3     CH(CH.sub.3)CO.sub.2 CH.sub.3                                                                  tert.-C.sub.4 H.sub.9                                                                     oil 1.46 (s; 9H)                                                               2.54 (s; 3H)                                                                   3.82 (s; 3H),                                                                  5.40(quart.; 1H)                                                               9.00(bs; 1H, NH)                   1325                                                                               CH.sub.3     2,6-Br.sub.2 -4-CNC.sub.6 H.sub.2                                                              tert.-C.sub.4 H.sub.9                                                                     143-146                            1326                                                                                ##STR43##   H               tert.-C.sub.4 H.sub.9                                                                     168-170                            1327                                                                                ##STR44##   H               tert.-C.sub.4 H.sub.9                                                                     157                                1328                                                                                ##STR45##   H               tert.-C.sub.4 H.sub.9                                                                     254                                1329                                                                                ##STR46##   CH.sub.3        tert.-C.sub.4 H.sub.9                                                                     oil 1.5 (s, 9H) 3.8; (s; 3H),                                                  .9 (s; 3H), 6.5 (d; 1H), 7.6                                                   (d; 1H), 8.7 (bs, 1H, NH)          1330                                                                                ##STR47##   CH.sub.3        tert.-C.sub.4 H.sub.9                                                                     120-122° C.                 1331                                                                                ##STR48##   CH.sub.3        tert.-C.sub.4 H.sub.9                                                                     oil, 1.5 (s; 9H), 3.7 (s;                                                      3H), 3.8 (s; 3H), 3.9 (s;                                                      3H), 8.0 (s; 1H), 9.2 (bs,                                                     1H, NH)                            1332                                                                                ##STR49##   H               tert.-C.sub.4 H.sub.9                         1333                                                                                ##STR50##   NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                         1334                                                                                ##STR51##   H               tert.-C.sub.4 H.sub.9                         1335                                                                                ##STR52##   NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                         1336                                                                               pyrid-2-yl   H               tert.-C.sub.4 H.sub.9                         1337                                                                               pyrid-2-yl   NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                         1338                                                                               pyrid-3-yl   H               tert.-C.sub.4 H.sub.9                         1339                                                                               pyrid-3-yl   NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                         1340                                                                               pyrid-4-yl   H               tert.-C.sub.4 H.sub.9                         1341                                                                               pyrid-4-yl   NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                         1342                                                                               4-FC.sub.6 H.sub.4CH.sub.2                                                                  H               tert.-C.sub.4 H.sub.9                         1343                                                                               4-FC.sub.6 H.sub.4CH.sub.2                                                                  NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                         1344                                                                               CH.sub.3     n-C.sub.4 H.sub.9                                                                              tert.-C.sub.4 H.sub.9                         1345                                                                               CH.sub.3     C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.9                         1346                                                                               CH.sub.3     tert.-C.sub.4 H.sub.9                                                                          tert.-C.sub.4 H.sub.9                         1347                                                                               C.sub.2 H.sub.5                                                                             n-C.sub.4 H.sub.9                                                                              tert.-C.sub.4 H.sub.9                         1348                                                                               C.sub.2 H.sub.5                                                                             C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.9                         1349                                                                               i-C.sub.3 H.sub.7                                                                           n-C.sub.4 H.sub.9                                                                              tert.-C.sub.4 H.sub.9                         1350                                                                               i-C.sub.3 H.sub.7                                                                           C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.9                         1351                                                                               i-C.sub.3 H.sub.7                                                                           cyclopentanimino                                                                               tert.-C.sub.4 H.sub. 9                                                                    113-115                            __________________________________________________________________________

                  TABLE 2                                                          ______________________________________                                          ##STR53##                                                                                                    mp [°C.]/.sup.1 H-NMR                    No.  R.sup.1 R.sup.5   R.sup.4 (CDCl.sub.3) [ppm]                              ______________________________________                                         2001 CH.sub.3                                                                               n-C.sub.4 H.sub.9                                                                        tert.-C.sub.4 H.sub.9                                   2002 CH.sub.3                                                                               C.sub.6 H.sub.5                                                                          tert.-C.sub.4 H.sub.9                                   2003 CH.sub.3                                                                               tert.-C.sub.4 H.sub.9                                                                    tert.-C.sub.4 H.sub.9                                                                  oil; 1.46 (s; 9H)                                                              1.60(s; 9H), 2.50 (s; 3H),                                                     7.94 (bs; 1H, NH)                               2004 C.sub.2 H.sub.5                                                                        n-C.sub.4 H.sub.9                                                                        tert.-C.sub.4 H.sub.9                                   2005 C.sub.2 H.sub.5                                                                        C.sub.6 H.sub.5                                                                          tert.-C.sub.4 H.sub.9                                   2006 i-C.sub.3 H.sub.7                                                                      C.sub.6 H.sub.5                                                                          tert.-C.sub.4 H.sub.9                                   2007 i-C.sub.3 H.sub.7                                                                      n-C.sub.4 H.sub.9                                                                        tert.-C.sub.4 H.sub.9                                   ______________________________________                                    

                  TABLE 3                                                          ______________________________________                                          ##STR54##                                                                                                           mp [°C.]/                                                               H-NMR                                                                          (CDCl.sub.3)                             No.  R.sup.1 R.sup.5         R.sup.4  [ppm]                                    ______________________________________                                         3001 CH.sub.3                                                                               H               i-C.sub.3 H.sub.7                                                                       153-154                                  3002 CH.sub.3                                                                               H               tert.-C.sub.4 H.sub.9                                                                   158-159                                  3003 CH.sub.3                                                                               H               C.sub.6 H.sub.5                                                                         178-183                                  3004 CH.sub.3                                                                               H               4-ClC.sub.6 H.sub.4                                                                     231                                      3005 CH.sub.3                                                                               H               3-CF.sub.3C.sub.6 H.sub.4                                                               221-223                                  3006 C.sub.2 H.sub.5                                                                        H               i-C.sub.3 H.sub.7                                                                       138-140                                  3007 C.sub.2 H.sub.5                                                                        CH.sub.3        i-C.sub.3 H.sub.7                                                                       55-56                                    3008 C.sub.2 H.sub.5                                                                        H               tert.-C.sub.4 H.sub.9                                                                   155-157                                  3009 C.sub.2 H.sub.5                                                                        CH.sub.3        tert.-C.sub.4 H.sub.9                                                                    39                                      3010 C.sub.2 H.sub.5                                                                        H               C.sub.6 H.sub.5                                                                         164                                      3011 C.sub.2 H.sub.5                                                                        CH.sub.3        C.sub.6 H.sub.5                                                                         130-131                                  3012 C.sub.2 H.sub.5                                                                        H               4-ClC.sub.6 H.sub.4                                                                     202-204                                  3013 C.sub.2 H.sub.5                                                                        CH.sub.3        4-ClC.sub.6 H.sub.4                                                                     158-159                                  3014 C.sub.2 H.sub.5                                                                        H               3-CF.sub.3C.sub.6 H.sub.4                                                               191-195                                  3015 C.sub.2 H.sub.5                                                                        CH.sub.3        3-CF.sub.3C.sub.6 H.sub.4                                                                84                                      3016 i-C.sub.3 H.sub.7                                                                      H               i-C.sub.3 H.sub.7                                                                       160-162                                  3017 i-C.sub.3 H.sub.7                                                                      CH.sub.3        i-C.sub.3 H.sub.7                                                                       90-91                                    3018 i-C.sub.3 H.sub.7                                                                      H               tert.-C.sub.4 H.sub.9                                                                   178-179                                  3019 i-C.sub.3 H.sub.7                                                                      CH.sub.3        tert.-C.sub.4 H.sub.9                                                                   38-41                                    3020 i-C.sub.3 H.sub.7                                                                      H               C.sub.6 H.sub.5                                                                         171-172                                  3021 i-C.sub.3 H.sub.7                                                                      CH.sub.3        C.sub.6 H.sub.5                                                                         92-93                                    3022 i-C.sub.3 H.sub.7                                                                      H               4-ClC.sub.6 H.sub.4                                                                     185-186                                  3023 i-C.sub.3 H.sub.7                                                                      CH.sub.3        4-ClC.sub.6 H.sub.4                                                                     92-93                                    3024 i-C.sub.3 H.sub.7                                                                      H               3-CF.sub.3C.sub.6 H.sub.4                                                               177-179                                  3025 i-C.sub.3 H.sub.7                                                                      CH.sub.3        3-CF.sub.3C.sub.6 H.sub.4                                                               37-45                                    3026 C.sub.6 H.sub.5                                                                        H               i-C.sub.3 H.sub.7                                                                       144                                      3027 C.sub.6 H.sub.5                                                                        CH.sub.3        i-C.sub.3 H.sub.7                                                                        98-100                                  3028 C.sub.6 H.sub.5                                                                        H               tert.-C.sub.4 H.sub.9                                                                   209                                      3029 C.sub.6 H.sub.5                                                                        CH.sub.3        tert.-C.sub.4 H.sub.9                                                                   130-131                                  3030 C.sub.6 H.sub.5                                                                        H               C.sub.6 H.sub.5                                                                         204                                      3031 C.sub.6 H.sub.5                                                                        CH.sub.3        C.sub.6 H.sub.5                                                                         100-101                                  3032 C.sub.6 H.sub.5                                                                        H               4-ClC.sub.6 H.sub.4                                                                     209                                      3033 C.sub.6 H.sub.5                                                                        CH.sub.3        4-ClC.sub.6 H.sub.4                                                                     157-158                                  3034 C.sub.6 H.sub.5                                                                        H               3-CF.sub.3C.sub.6 H.sub.4                                                               217                                      3035 C.sub.6 H.sub.5                                                                        CH.sub.3        3-CF.sub.3C.sub.6 H.sub.4                                                               131-132                                  3036 i-C.sub.3 H.sub.7                                                                      succinimido     i-C.sub.3 H.sub.7                                                                        98-100                                  3037 i-C.sub.3 H.sub.7                                                                      succinimido     tert.-C.sub.4 H.sub.9                                                                   75-76                                    3038 i-C.sub.3 H.sub.7                                                                      Na.sup.⊕    tert.-C.sub.4 H.sub.9                                                                   300                                      3039 i-C.sub.3 H.sub.7                                                                      K.sup.⊕     tert.-C.sub.4 H.sub.9                                                                   110                                      3040 i-C.sub.3 H.sub.7                                                                      Na.sup.⊕    C.sub.6 H.sub.5                                                                         330                                      3041 i-C.sub.3 H.sub.7                                                                      K.sup.⊕     C.sub.6 H.sub.5                                                                         300                                      3042 i-C.sub.3 H.sub.7                                                                       ##STR55##      C.sub.6 H.sub.5                                                                         154-157                                  3043 i-C.sub.3 H.sub.7                                                                       ##STR56##      C.sub.6 H.sub.5                                                                         162-164                                  3044 i-C.sub.3 H.sub.7                                                                      succinimido     C.sub.6 H.sub.5                                                                         161                                      3045 CH.sub.3                                                                               NC(CH.sub.3).sub.2                                                                             tert.-C.sub.4 H.sub.9                                                                   97-98                                    ______________________________________                                    

Other compounds, for instance, having the general structure ##STR57## may be prepared analogously in which X and Y are oxygen or sulfur, e.g., R¹ is a radical from the group Q1 to Q61,

R⁵ is a radical from the group M1 to M78,

R³ is a radical from the group P₁ -P₁₁

R⁴ is a radical from the group L1 to L195, and

the radicals X, Y, P, Q, M and L may be combined at will.

R¹, R⁵, R³ and R⁴ may be for example denote the following radicals:

    ______________________________________                                         Comp.                 Comp.                                                    No.   R.sup.1         No.     R.sup.1                                          ______________________________________                                         Q1    H               Q24     tetrahydro-                                      Q2    CH.sub.3                pyran-3-yl                                       Q3    C.sub.2 H.sub.5 Q25     tetrahydropyran-3-yl                             Q4    n-C.sub.3 H.sub.7                                                                              Q26     C.sub.6 H.sub.5                                  Q5    i-C.sub.3 H.sub.7                                                                              Q27     2-FC.sub.6 H.sub.4                               Q6    n-C.sub.4 H.sub.9                                                                              Q28     3-FC.sub.6 H.sub.4                               Q7    i-C.sub.4 H.sub.9                                                                              Q29     4-FC.sub.6 H.sub.4                               Q8    s-C.sub.4 H.sub.9                                                                              Q30     2-ClC.sub.6 H.sub.4                              Q9    tert.-C.sub.4 H.sub.9                                                                          Q31     3-ClC.sub.6 H.sub.4                              Q10   cyclo-C.sub.3 H.sub.5                                                                          Q32     4-ClC.sub.6 H.sub.4                              Q11   cyclo-C.sub.4 H.sub.7                                                                          Q33     2-CH.sub.3C.sub.6 H.sub.4                        Q12   cyclo-C.sub.5 H.sub.9                                                                          Q34     3-CH.sub.3C.sub.6 H.sub.4                        Q13   cyclo-C.sub.6 H.sub.11                                                                         Q35     4-CH.sub.3C.sub.6 H.sub.4                        Q14   cyclo-C.sub.7 H.sub.13                                                                         Q36     2-CF.sub.3C.sub.6 H.sub.4                        Q15   cyclo-C.sub.8 H.sub.15                                                                         Q37     3-CF.sub.3C.sub.6 H.sub.4                        Q16   CF.sub.3        Q38     4-CF.sub.3C.sub.6 H.sub.4                        Q17   CH.sub.2 OCH.sub.3                                                                             Q39     2-OCH.sub.3C.sub.6 H.sub.4                       Q18   CH(CH.sub.3)OCH.sub.3                                                                          Q40     3-OCH.sub. 3C.sub.6 H.sub.4                      Q19   CH(CH.sub.3)CH.sub.2 OCH.sub.3                                                                 Q41     4-OCH.sub.3C.sub.6 H.sub.4                       Q20   CH.sub.2 OC.sub.2 H.sub.5                                                                      Q42     4-OCF.sub.3C.sub.6 H.sub.4                       Q21   tetrahydrofur-2-yl                                                                             Q43     4-SCH.sub.3C.sub.6 H.sub.4                       Q22   tetrahydrofur-2-yl                                                                             Q44     4-SCF.sub.3C.sub.6 H.sub.4                       Q23   tetrahydrofur-2-yl                                                                             Q45     4-NO.sub.2C.sub.6 H.sub.4                        Q47   neo-C.sub.5 H.sub.11                                                                           Q46     4-CNC.sub.6 H.sub.4                              Q48   CH.sub.3 O      Q56                                                                                     ##STR58##                                       Q49   C.sub.2 H.sub.5 O                                                                              Q57                                                                                     ##STR59##                                       Q50   C.sub.6 H.sub.5CH.sub.2                                                                        Q58                                                                                     ##STR60##                                       Q51   4-FC.sub.6 H.sub.4CH.sub.2                                                                     Q59     pyrid-2-yl                                       Q51   4-CH.sub.3C.sub.6 H.sub.4CH.sub.2                                                              Q60     pyrid-3-yl                                       Q52                                                                                   ##STR61##      Q61     pyrid-4-yl                                       Q53                                                                                   ##STR62##      Q62     2,6-F.sub.2C.sub.6 H.sub.3                       Q54                                                                                   ##STR63##                                                               Q55                                                                                   ##STR64##                                                               ______________________________________                                    

    ______________________________________                                         Comp. No.       R.sup.5                                                        ______________________________________                                         M1              H                                                              M2              CH.sub.3                                                       M3              C.sub.2 H.sub.5                                                M4              n-C.sub.3 H.sub.7                                              M5              i-C.sub.3 H.sub.7                                              M6              n-C.sub.4 H.sub.9                                              M7              s-C.sub.4 H.sub.9                                              M8              t-C.sub.4 H.sub.9                                              M9              CH(CH.sub.3)C.sub.6 H.sub.13                                   M10             CH.sub.2 CH.sub.2 OCH.sub.3                                    M11             CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5                             M12             succinimido                                                    M13             Li.sup.⊕                                                   M14             Na.sup.⊕                                                   M15             K.sup.⊕                                                    M16             NH.sub.4.sup.⊕                                             M17             H.sub.3 N.sup.⊕ i-C.sub.3 H.sub.7                          M18             H.sub.2 N.sup.⊕ (i-C.sub.3 H.sub.7).sub.2                  M19             H.sub.3 N.sup.⊕ CH.sub.2 CH.sub.2 OH                       M20             CH.sub.2 CHCH.sub.2                                            M21             CH.sub.2C(CH.sub.3)CH.sub.2                                    M22             CH.sub.2C(Cl)CH.sub.2                                          M23             CH.sub.2CCH                                                    M24             CH.sub.2CCCH.sub.2 OH                                          M25             NC(CH.sub.3).sub.2                                             M26             NC(C.sub.2 H.sub.5).sub.2                                      M27             CH.sub.2 CH.sub.2N(CH.sub.3).sub.2                             M28             CH.sub.2CH.sub.2N(C.sub.2 H.sub.5).sub.2                       M29             CH.sub.2CH.sub.2 N.sup.⊕ (CH.sub.3).sub.3 I.sup..crclb                     ar.                                                            M30             CH.sub.2CF.sub.3                                               M31             phenyl                                                         M32             phenylethyl                                                    M33             CH.sub.2CH.sub.2Si(CH.sub.3).sub.3                             M34             CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2                            M35             CH.sub.2PO(OC.sub.2 H.sub.5).sub.2                             M36             CH(CH.sub.3)CH(OCH.sub.3).sub.2                                M37             CH.sub.2CON(C.sub.2 H.sub.5).sub.2                             M38             N(C.sub.2 H.sub.5).sub.2                                       M39             CH.sub.2OCH.sub.2C.sub.6 H.sub.5                               M40             CH(COOCH.sub.3).sub.2                                          M41             NC(cyclo-C.sub.3 H.sub.5).sub.2                                M42                                                                                             ##STR65##                                                     M43             cyclohexanimino                                                M44             cyclooctanimino                                                M45             CH.sub.2CH.sub.2Cl                                             M46             CH.sub.2CH.sub.2CN                                             M47             CH.sub.2CCl.sub.3                                              M48             pyrid-3-ylmethyl                                               M49             thien-2-yl-methyl                                              M50                                                                                             ##STR66##                                                     M51                                                                                             ##STR67##                                                     M52                                                                                             ##STR68##                                                     M53             CH(C.sub.6 H.sub.5)COOCH.sub.3                                 M54             cyclo-C.sub.6 H.sub.11                                         M55             CH.sub.2OCH.sub.2C.sub.6 H.sub.5                               M56             tetrahydropyran-2-yl                                           M57             tetrahydrofur-2-yl                                             M58             (4-bromobenzoyl)methyl                                         M59             (4-methoxybenzoyl)methyl                                       M60             CH(COOCH.sub.3).sub.2                                          M61             phthalimidomethyl                                              M62             fur-2-ylmethyl                                                 M63             tetrahydrofur-2-yl-methyl                                      M64             pyrid-2-ylmethyl                                               M65             pyrid-4-ylmethyl                                               M66             pyrid-3-yl-methyl                                              M67             thien-2-yl-methyl                                              M68             CH(C.sub.6 H.sub.5)COOCH.sub.3                                 M69             piperidino                                                     M70             phthalimido                                                    M71                                                                                             ##STR69##                                                     M72             NCHC.sub.6 H.sub.5                                             M73                                                                                             ##STR70##                                                     M74             2-NO.sub.2 -4-FC.sub.6 H.sub.3                                 M75             3,5-(CF.sub.3).sub.2C.sub.6 H.sub.3                            M76             CH.sub.2CH.sub.2SCH.sub.3                                      M77             4-NHCOCH.sub.3C.sub.6 H.sub.4                                  M78             2,4-dichlorobenzyl                                             ______________________________________                                    

    ______________________________________                                         Comp.               Comp.                                                      No.      R.sup.3    No.       R.sup.3                                          ______________________________________                                         P1       H          P12       CH.sub.2 OC.sub.2 H.sub.5                        P2       CH.sub.3   P13       CH.sub.2 CH.sub.2 OCH.sub.3                      P3       C.sub.2 H.sub.5                                                                           P14       CH.sub.2 SCH.sub.3                               P4       n-C.sub.3 H.sub.7                                                                         P15       CH.sub.2 SC.sub.2 H.sub.5                        P5       i-C.sub.3 H.sub.7                                                                         P16       CH.sub.2 CH.sub.2 SCH.sub.3                      P6       n-C.sub.4 H.sub.9                                                                         P17       CH.sub.2 -CH.sub.2 -N(CH.sub.3).sub.2            P7       s-C.sub.4 H.sub.9                                                                         P18       CH.sub.2 CH.sub.2 -N(C.sub.2 H.sub.5).sub.2      P8       t-C.sub.4 H.sub.9                                                                         P19       cyclo-C.sub.3 H.sub.5                            P9       CH.sub.2 -CH.sub.2 OH                                                                     P20       cyclo-C.sub.6 H.sub.11                           P10      CH.sub.2 -CH.sub.2 Cl                                                                     P21       1-methyl-cyclo-C.sub.6 H.sub.10                  P11      CH.sub.2 OCH.sub.3                                                    ______________________________________                                    

    ______________________________________                                         Comp. No.      R.sup.4                                                         ______________________________________                                         L1             H                                                               L2             CH.sub.3                                                        L3             C.sub.2 H.sub.5                                                 L4             n-C.sub.3 H.sub.7                                               L5             i-C.sub.3 H.sub.7                                               L6             n-C.sub.4 H.sub.9                                               L7             i-C.sub.4 H.sub.9                                               L8             sec-C.sub.4 H.sub.9                                             L9             tert.-C.sub.4 H.sub.9                                           L10            n-C.sub.5 H.sub.11                                              L11            CH(CH.sub.3)C.sub.3 H.sub.7                                     L12            CH(C.sub.2 H.sub.5)C.sub.2 H.sub.5                              L13            n-C.sub.6 H.sub.13                                              L14            CH(CH.sub.3)C.sub.4 H.sub.9                                     L15            CH(C.sub.2 H.sub.5)C.sub.3 H.sub.7                              L16            n-C.sub.7 H.sub.15                                              L17            CH(CH.sub.3)C.sub.5 H.sub.11                                    L18            CH(C.sub.2 H.sub.5)C.sub.4 H.sub.9                              L19            n-C.sub.8 H.sub.17                                              L20            CH(CH.sub.3)C.sub.6 H.sub.13                                    L21            CH(C.sub.2 H.sub.5)C.sub.5 H.sub.11                             L22            C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub.3                    L23            cyclo-C.sub.3 H.sub.5                                           L24            cyclo-C.sub.4 H.sub.7                                           L25            cyclo-C.sub.5 H.sub.9                                           L26            cyclo-C.sub.6 H.sub.11                                          L27            cyclo-C.sub.7 H.sub.13                                          L28            cyclo-C.sub.8 H.sub.15                                          L29            1-methylcyclohexyl                                              L30            1-ethylcyclohexyl                                               L31            3,5-dimethylcyclohexyl                                          L32            3-trifluoromethylcyclohexyl                                     L33            tetrahydropyran-4-yl                                            L34            4-methyl-tetrahydropyran                                        L35            4-methyl-tetrahydropyran-4-yl                                   L36            CH.sub.2CHCH.sub.2                                              L37            CH(CH.sub.3)CHCH.sub.2                                          L38            C(CH.sub.3).sub.2 CHCH.sub.2                                    L39            C(CH.sub.3, C.sub.2 H.sub.5)CHCH.sub.2                          L40            C(CH.sub.3).sub.2C.sub.2 H.sub.5                                L41            C(CH.sub.3, C.sub.2 H.sub.5)C.sub.2 H.sub.5                     L42            C(CH.sub.3).sub.2 C.sub.3 H.sub.7                               L43            C(CH.sub.3).sub.2 cycloC.sub.6 H.sub.11                         L44            CH.sub.2C(CH.sub.3)CH.sub.2                                     L45            CH.sub.2 CHCHCH.sub.3                                           L46            CH(CH.sub.3)CHCHCH.sub.3                                        L47            C(CH.sub.3).sub.2 CHCHCH.sub.3                                  L48            CH.sub.2 CCH                                                    L49            CH(CH.sub.3)CCH                                                 L50            C(CH.sub.3).sub.2 CCH                                           L51            C(CH.sub.3, C.sub.2 H.sub.5)CCH                                 L52            C(C.sub.2 H.sub.5).sub.2 CCH                                    L53            CH.sub.2 CCCH.sub.3                                             L54            CH(CH.sub.3 )CCCH.sub.3                                         L55            C(CH.sub.3).sub.2 CCCH.sub.3                                    L56            CH.sub.2 C.sub.6 H.sub.5                                        L57            CH(CH.sub.3)C.sub.6 H.sub.5                                     L58            C(CH.sub.3).sub.2 C.sub.6 H.sub.5                               L59            CH.sub.2 CH.sub.2 C.sub.6 H.sub.5                               L60            CH.sub.2 CH.sub.2 SCH.sub.3                                     L61            CH(CH.sub.3)CH.sub.2 SCH.sub.3                                  L62            C(CH.sub.3).sub.2 CH.sub.2 SCH.sub.3                            L63            CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3                            L64            CH.sub.2 CH.sub.2 Cl                                            L65            CH(CH.sub.3)CH.sub.2 Cl                                         L66            C(CH.sub.3).sub.2 CH.sub.2 Cl                                   L67            CH.sub.2 CH.sub.2 OCH.sub.3                                     L68            CH(CH.sub.3)CH.sub.2 OCH.sub.3                                  L69            C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3                            L70            CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                             L71            CH.sub.2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2                      L72            CH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.3                            L73            CH.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                    L74            CH.sub.2 CH.sub. 2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2            L75            2-CH.sub.3C.sub.6 H.sub.4                                       L76            3-CH.sub.3C.sub.6 H.sub.4                                       L77            4-CH.sub.3C.sub.6 H.sub.4                                       L78            2-C.sub.2 H.sub.5C.sub.6 H.sub.4                                L79            3-C.sub.2 H.sub.5C.sub.6 H.sub.4                                L80            4-C.sub.2 H.sub.5C.sub.6 H.sub.4                                L81            3-tert.-C.sub.4 H.sub.9C.sub.6 H.sub.4                          L82            4-tert.-C.sub.4 H.sub.9C.sub.6 H.sub.4                          L83            2,3-(CH.sub.3).sub.2C.sub.6 H.sub.3                             L84            2,4-(CH.sub.3).sub.2C.sub.6 H.sub.3                             L85            2,5-(CH.sub.3).sub.2C.sub.6 H.sub.3                             L86            2,6-(CH.sub.3).sub.2C.sub.6 H.sub.3                             L87            3,4-(CH.sub.3).sub.2C.sub.6 H.sub.3                             L88            3,5-(CH.sub.3).sub.2C.sub.6 H.sub.3                             L89            2,3,4-(CH.sub.3).sub.3C.sub.6 H.sub.2                           L90            2,3,5-(CH.sub.3).sub.3C.sub.6 H.sub.2                           L91            2,4,5-(CH.sub.3).sub.3C.sub.6 H.sub.2                           L92            2,4,6-(CH.sub.3).sub.3C.sub.6 H.sub.2                           L93            3,4,5-(CH.sub.3).sub.3C.sub.6 H.sub.2                           L94            2-CF.sub.3C.sub.6 H.sub.4                                       L95            3-CF.sub.3C.sub.6 H.sub.4                                       L96            4-CF.sub.3C.sub.6 H.sub.4                                       L97            2-FC.sub.6 H.sub. 4                                             L98            3-FC.sub.6 H.sub.4                                              L99            4-FC.sub.6 H.sub.4                                              L100           2-ClC.sub.6 H.sub.4                                             L101           3-ClC.sub.6 H.sub.4                                             L102           4-ClC.sub.6 H.sub.4                                             L103           2-BrC.sub.6 H.sub.4                                             L104           3-BrC.sub.6 H.sub.4                                             L105           4-BrC.sub.6 H.sub.4                                             L106           2,3-F.sub.2C.sub.6 H.sub.3                                      L107           2,4-F.sub.2C.sub.6 H.sub.3                                      L108           2,5-F.sub.2C.sub.6 H.sub.3                                      L109           2,6-F.sub.2C.sub.6 H.sub.3                                      L110           2,3-Cl.sub.2C.sub.6 H.sub.3                                     L111           2,4-Cl.sub.2C.sub.6 H.sub.3                                     L112           2,5-Cl.sub.2C.sub.6 H.sub.3                                     L113           2,6-Cl.sub.2C.sub.6 H.sub.3                                     L114           3,4-Cl.sub.2C.sub.6 H.sub.3                                     L115           3,5-Cl.sub.2C.sub.6 H.sub.3                                     L116           2,3,4-Cl.sub.3C.sub.6 H.sub.2                                   L117           2,3,5-Cl.sub.3C.sub.6 H.sub.2                                   L118           2,4,6-Cl.sub.3C.sub.6 H.sub.2                                   L119           3,4,5-Cl.sub.3C.sub.6 H.sub.2                                   L120           2-CNC.sub.6 H.sub.4                                             L121           3-CNC.sub.6 H.sub.4                                             L122           4-CNC.sub.6 H.sub.4                                             L123           2-OCH.sub.3C.sub.6 H.sub.4                                      L124           3-OCH.sub.3C.sub.6 H.sub.4                                      L125           4-OCH.sub.3C.sub.6 H.sub.4                                      L126           2-OC.sub.2 H.sub.5C.sub.6 H.sub.4                               L127           3-OC.sub.2 H.sub.5 C.sub.6 H.sub.4                              L128           4-OC.sub.2 H.sub.5C.sub.6 H.sub.4                               L129           2-O-n-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L130           3-O-n-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L131           4-O-n-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L132           2-O-i-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L133           3-O-i-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L134           4-O-i-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L135           2,3-(OCH.sub.3).sub.2C.sub.6 H.sub.3                            L136           2,4-(OCH.sub.3).sub.2C.sub.6 H.sub.3                            L137           2,5-(OCH.sub.3).sub.2C.sub.6 H.sub.3                            L138           2,6-(OCH.sub.3).sub.2C.sub.6 H.sub.3                            L139           3,4-(OCH.sub.3).sub.2C.sub.6 H.sub.3                            L140           3,5-(OCH.sub.3).sub.2C.sub.6 H.sub.3                            L141           3,4,5-(OCH.sub.3).sub.3C.sub.6 H.sub.2                          L142           2-OCF.sub.3C.sub.6 H.sub.4                                      L143           3-OCF.sub.3C.sub.6 H.sub.4                                      L144           4-OCF.sub.3C.sub.6 H.sub.4                                      L145           2-OCF.sub.2 CHF.sub.2C.sub.6 H.sub.4                            L146           3-OCF.sub.2 CHF.sub.2C.sub.6 H.sub.4                            L147           4-OCF.sub.3 CHF.sub.2C.sub.6 H.sub.4                            L148           2-SCH.sub.3C.sub.6 H.sub.4                                      L149           3-SCH.sub.3C.sub.6 H.sub.4                                      L150           4-SCH.sub.3C.sub.6 H.sub.4                                      L151           2-SC.sub.2 H.sub.5C.sub.6 H.sub.4                               L152           3-SC.sub.2 H.sub.5C.sub.6 H.sub.4                               L153           4-SC.sub.2 H.sub.5C.sub.6 H.sub.4                               L154           2-S-i-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L155           3-S-i-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L156           4-S-i-C.sub.3 H.sub.7C.sub.6 H.sub.4                            L157           2,4-(SCH.sub.3).sub.2C.sub.6 H.sub.3                            L158           2-SCF.sub.3C.sub.6 H.sub.4                                      L159           3-SCF.sub.3C.sub.6 H.sub.4                                      L160           4-SCF.sub.3C.sub.6 H.sub.4                                      L161           2-NO.sub.2C.sub.6 H.sub.4                                       L162           3-NO.sub.2C.sub.6 H.sub.4                                       L163           4-NO.sub.2C.sub.6 H.sub.4                                       L164           2,3-(NO.sub.2).sub.2C.sub.6 H.sub.3                             L165           2,4-(NO.sub.2).sub.2C.sub.6 H.sub.3                             L166           2,5-(NO.sub.2).sub.2C.sub.6 H.sub.3                             L167           2,6-(NO.sub.2).sub.2C.sub.6 H.sub.3                             L168           3,4-(NO.sub.2).sub.2C.sub.6 H.sub.3                             L169           3,5-(NO.sub.2).sub.2C.sub.6 H.sub.3                             L170           2-CHOC.sub.6 H.sub.4                                            L171           3-CHOC.sub.6 H.sub.4                                            L172           4-CHOC.sub.6 H.sub.4                                            L173                                                                                           ##STR71##                                                      L174                                                                                           ##STR72##                                                      L175                                                                                           ##STR73##                                                      L176                                                                                           ##STR74##                                                      L177                                                                                           ##STR75##                                                      L178                                                                                           ##STR76##                                                      L179                                                                                           ##STR77##                                                      L180                                                                                           ##STR78##                                                      L181                                                                                           ##STR79##                                                      L182                                                                                           ##STR80##                                                      L183                                                                                           ##STR81##                                                      L184                                                                                           ##STR82##                                                      L185           1-naphthyl                                                      L186           2-naphthyl                                                      L187           C.sub.6 H.sub.5                                                 L188           piperidino                                                      L189           tetrahydrofur-3-yl                                              L190           thiazol-2-yl                                                    L191           5-methyl-thiazol-2-yl                                           L192           5-ethyl-thiazol-2-yl                                            L193           5-n-propyl-thiazol-2-yl                                         L194           4-methyl-5-carboxy-thiazol-2-yl                                 L195           cyclopropylmethyl                                               ______________________________________                                    

The compounds Ia, or the herbicidal agents containing them, may be applied for instance in the form of directly sprayable solutions, powders, suspensions (including high-percentage aqueous, oily or other suspensions), dispersions, emulsions, oil dispersions, pastes, dusts, broadcasting agents, or granules by spraying, atomizing, dusting, broadcasting or watering. The forms of application depend entirely on the purpose for which the agents are being used, but they must ensure as fine a distribution of the active ingredients according to the invention as possible.

For the preparation of solutions, emulsion, pastes and oil dispersions to be sprayed direct, mineral oil fractions of medium to high boiling point, such as kerosene or diesel oil, further coal-tar oils, and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons such as benzene, toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes and their derivatives such as methanol, ethanol, propanol, butanol, chloroform, carbon tetrachloride, cyclohexanol, cyclohexanone, chlorobenzene, isophorone, etc., and strongly polar solvents such as dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, water, etc. are suitable.

Aqueous formulations may be prepared from emulsion concentrates, pastes dispersions, wettable powders or water-dispersible granules by adding water. To prepare emulsions, pastes and oil dispersions the ingredients as such or dissolved in an oil or solvent may be homogenized in water by means of wetting or dispersing agents, adherents or emulsifiers. Concentrates which are suitable for dilution with water may be prepared from active ingredient, wetting agent, adherent, emulsifying or dispersing agent and possibly solvent or oil.

Examples of surfactants are: alkali metal, alkaline earth metal and ammonium salts of ligninsulfonic acid, naphthalenesulfonic acids, phenolsulfonic acids, alkylaryl sulfonates, alkyl sulfates, and alkyl sulfonates, alkali metal and alkaline earth metal salts of dibutylnaphthalenesulfonic acid, lauryl ether sulfate, fatty alcohol sulfates, alkali metal and alkaline earth metal salts of fatty acids, salts of sulfated hexadecanols, heptadecanols, and octadecanols, salts of sulfated fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol, ethoxylated octylphenol and ethoxylated nonylphenol, alkylphenol polyglycol ethers, tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignin, sulfite waste liquors and methyl cellulose.

Powders, dusts and broadcasting agents may be prepared by mixing or grinding the active ingredients with a solid carrier.

Granules, e.g., coated, impregnated or homogeneous granules, may be prepared by bonding the active ingredients to solid carriers. Examples of solid carriers are mineral earths such as silicic acid, silica gels, silicates, talc, kaolin, attapulgus clay, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, and ureas, and vegetable products such as grain flours, bark meal, wood meal, and nutshell meal, cellulosic powders, etc.

Examples of such formulations are as follows:

I. 90 parts by weight of compound no. 1006 is mixed with 10 parts by weight of N-methyl-alpha-pyrrolidone. A mixture is obtained which is suitable for application in the form of very fine drops.

II. 20 parts by weight of compound no. 1006 is dissolved in a mixture consisting of 80 parts by weight of xylene, 10 parts by weight of the adduct of 8 to 10 moles of ethylene oxide and 1 mole of oleic acid-N-monoethanolamide, 5 parts by weight of the calcium salt of dodecylbenzene-sulfonic acid, and 5 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil. By pouring the solution into water and uniformly distributing it therein, an aqueous dispersion is obtained.

III. 20 parts by weight of compound no. 1002 is dissolved in a mixture consisting of 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts by weight of the adduct of 7 moles of ethylene oxide and 1 mole of isooctylphenol, and 10 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil. By pouring the solution into 100,000 parts by weight of water and finely distributing it therein, an aqueous dispersion is obtained containing 0.2% by weight of the active ingredient.

IV. 20 parts by weight of compound no. 1049 is dissolved in a mixture consisting of 25 parts by weight of cyclohexanol, 65 parts by weight of a mineral oil fraction having a boiling point between 210° and 280° C., and 10 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil. By pouring the solution into 100,000 parts by weight of water and uniformly distributing it therein, an aqueous dispersion is obtained containing 0.02% by weight of the active ingredient.

V. 20 parts by weight of compound no. 3038 is well mixed with 3 parts by weight of the sodium salt of diisobutylnaphthalene-alpha-sulfonic acid, 17 parts by weight of the sodium salt of a lignin-sulfonic acid obtained from a sulfite waste liquor, and 60 parts by weight of powdered silica gel, and triturated in a hammer mill. By uniformly distributing the mixture in 20,000 parts by weight of water, a spray liquor is obtained containing 0.1% by weight of the active ingredient.

VI. 3 parts by weight of compound no. 1075 is intimately mixed with 97 parts by weight of particulate kaolin. A dust is obtained containing 3% by weight of the active ingredient.

VII. 30 parts by weight of compound no. 1220 is intimately mixed with a mixture consisting of 92 parts by weight of powered silica gel and 8 parts by weight of paraffin oil which has been sprayed onto the surface of this silica gel. A formulation of the active ingredient is obtained having good adherence.

VIII. 20 parts of compound no. 1026 is intimately mixed with 2 parts of the calcium salt of dodecylbenzenesulfonic acid, 8 parts of a fatty alcohol polyglycol ether, 2 parts of the sodium salt of a phenolsulfonic acid-urea-formaldehyde condensate and 68 parts of a paraffinic mineral oil. A stable oily dispersion is obtained.

The formulations contain from 0.1 to 95, and preferably 0.5 to 90, % by weight of active ingredient.

The active ingredients may be applied pre- or (preferably) postemergence. If certain crop plants tolerate the active ingredients less well, application techniques may be used in which the herbicidal agents are sprayed from suitable equipment in such a manner that the leaves of sensitive crop plants are if possible not touched, and the agents reach the soil or the unwanted plants growing beneath the crop plants (post-directed, lay-by treatment).

The application rates depend on the objective to be achieved, the time of the year, the plants to be combated and their growth stage, and are from 0.001 to 5.0, preferably 0.01 to 1.0, kg of active ingredient per hectare.

In view of the spectrum of unwanted plants which can be combated, the tolerance of the novel compounds by crop plants, and in view of the number of application methods possible, the compounds of the formula Ia, or agents containing them, may be used in a further large number of crops for removing unwanted plants. The following crops are given by way of example:

    __________________________________________________________________________     Botanical name           Common name                                           __________________________________________________________________________     Allium cepa              onions                                                Ananas comosus           pineapples                                            Arachis hypogaea         peanuts (groundnuts)                                  Asparagus officinalis    asparagus                                             Avena sativa             oats                                                  Beta vulgaris spp. altissima                                                                            sugarbeets                                            Beta vulgaris spp. rapa  fodder beets                                          Beta vulgaris spp. esculenta                                                                            table beets, red beets                                Brassica napus var. napus                                                                               rapeseed                                              Brassica napus var. napobrassica                                                                        swedes                                                Brassica napus var. rapa turnips                                               Brassica rapa var. silvestris                                                  Camellia sinensis        tea plants                                            Carthamus tinctorius     safflower                                             Carya illinoinensis      pecan trees                                           Citrus limon             lemons                                                Citrus maxima            grapefruits                                           Citrus reticulata        mandarins                                             Citrus sinensis          orange trees                                          Coffea arabica (Coffea canephora,                                                                       coffee plants                                         Coffea liberica)                                                               Cucumis melo             melons                                                Cucumis sativus          cucumbers                                             Cynodon dactylon         Bermudagrass                                          Elais guineensis         oil palms                                             Fragaria vesca           strawberries                                          Glycine max              soybeans                                              Gossypium hirsutum (Gossypium arboreum,                                                                 cotton                                                Gossypium herbaceum, Gossypium vitifolium)                                     Helianthus annuus        sunflowers                                            Helianthus tuberosus     Jerusalem artichoke                                   Hevea brasiliensis       rubber plants                                         Hordeum vulgare          barley                                                Humulus lupulus          hops                                                  Ipomoea batatas          sweet potatoes                                        Juglans regia            walnut trees                                          Lactuca sativa           lettuce                                               Lens culinaris           lentils                                               Linum usitatissimum      flax                                                  Lycopersicon lycopersicum                                                                               tomatoes                                              Malus spp.               apple trees                                           Manihot esculanta        cassava                                               Medicago sativa          alfalfa (lucerne)                                     Mentha piperita          peppermint                                            Musa spp.                banana plants                                         Nicotiana tabacum (N. rustica)                                                                          tobacco                                               Olea europaea            olive trees                                           Oryza sativa             rice                                                  Panicum miliaceum        millet                                                Phaseolus lunatus        limabeans                                             Phaseolus mungo          mungbeans                                             Phaseolus vulgaris       snapbeans, green beans,                                                        dry beans                                             Pennisetum glaucum       pearl millet                                          Petroselinum crispum spp. tuberosum                                                                     parsley                                               Picea abies              Norway spruce                                         Abies alba               fir trees                                             Pinus spp.               pine trees                                            Pisum sativum            English peas                                          Prunus avium             cherry trees                                          Prunus domestica         plum trees                                            Prunus dulcis            almond trees                                          Prunus persica           peach trees                                           Pyrus communis           pear trees                                            Ribes sylvestre          redcurrants                                           Ribes uva-crispa         gooseberries                                          Ricinus communis         castor-oil plants                                     Saccharum officinarum    sugar cane                                            Secale cereale           rye                                                   Sesamum indicum          sesame                                                Solanum tuberosum        Irish potatoes                                        Sorghum bicolor (s. vulgare)                                                                            sorghum                                               Sorghum dochna           sorgo                                                 Spinacia oleracea        spinach                                               Theobroma cacao          cacao plants                                          Trifolium pratense       red clover                                            Triticum aestivum        Wheat                                                 Triticum durum           durum wheat                                           Vaccinium corymbosum     blueberries                                           Vaccinium vitis-idaea    cranberries                                           Vicia faba               tick beans                                            Vigna sinensis (V. unguiculata)                                                                         cow peas                                              __________________________________________________________________________     Vitis vinifera           grapes                                                Zea mays                 Indian corn, sweet corn,                                                       maize                                                 __________________________________________________________________________

To increase the spectrum of action and to achieve synergistic effects, the isoxazole-(isothiazole)-5-carboxamides of the formula Ia may be mixed and applied together with numerous representatives of other herbicidal or growth-regulating active ingredient groups. Examples of suitable components are diazines, 4H-3,1-benzoxazine derivatives, benzothiadiazinones, 2,6-dinitroanilines, N-phenylcarbamates, thiolcarbamates, halocarboxylic acids, triazines, amides, ureas, diphenyl ethers, triazinones, uracils, benzofuran derivatives, cyclohexane-1,3-dione derivatives, quinolinecarboxylic acids, sulfonylureas, imidazolinones, (hetero)aryloxyphenylpropionic acids and salts, esters and amides thereof, etc.

It may also be useful to apply the compounds of the formula Ia, either alone or in combination with other herbicides, in admixture with other crop protecting agents, e.g., agents for combating pests or phytopathogenic fungi or bacteria. The compounds may also be mixed with solutions of mineral salts used to remedy nutritional or trace element deficiencies. Non-phytotoxic oils and oil concentrates may also be added.

USE EXAMPLES

The action of the isoxazole-(isothiazole)-5-carboxamides of the formula Ia on plant growth is demonstrated in greenhouse experiments.

The vessels employed were plastic flowerpots having a volume of 300 cm³ and filled with a sandy loam containing about 3.0% humus. The seeds of the test plants were sown separately, according to species.

For the preemergence treatment, the formulated active ingredients were applied to the surface of the soil immediately after the seeds had been sown. The compounds were emulsified or suspended in water as vehicle, and sprayed through finely distributing nozzles. The application rate was 0.5 kg of active ingredient per hectare. After the agents had been applied, the vessels were lightly sprinkler-irrigated to induce germination and growth. Transparent plastic covers were then placed on the vessels until the plants had taken root. The cover ensured uniform germination of the plants, insofar as this was not impaired by the active ingredients.

For postemergence treatment, either plants which had been sown in the pots and grown there were selected, or they were cultivated separately as seedlings and transplanted to the pots a few days before being treated.

The plants were grown, depending on growth form, to a height of 3 to 15 cm before being treated with the active ingredients, which were suspended or emulsified in water as vehicle, and sprayed through finely distributing nozzles. The application rates for postemergence treatment were 1.0 and 3.0 kg/ha.

The pots were set up in the greenhouse, species from warmer climates in warmer areas (20° to 35° C.) and species from moderate climates at 10° to 25° C. The experiments were run for from 2 to 4 weeks. During this time the plants were tended and their reactions to the various treatments assessed. The assessment scale was 0, to 100, 100 denoting nonemergence or complete destruction of at least the visible plant parts, and 0 denoting no damage or normal growth.

The plants used in the greenhouse experiments were Abutilon theophrasti, Centaurea cyanus, Chenopodium album, Chrysanthemum coronarium, Echinochloa crus-galli, Galium aparine, Ipomoea spp., Lolium multiflorum, Mentha piperita, Mercurialis annua, Solanum nigrum, Triticum aestivum, Viola spp. and Zea mays.

Active ingredient no. 1006 selected by way of example combated unwanted plants excellently on preemergence application of 3.0 kg/ha.

For example compounds nos. 1004, 1014, 3018, 1026, 1006, 1049 and 1022 had, on postemergence application of 1 to 3 kg/ha, a herbicidal action on a broad spectrum of unwanted plants. Compounds nos. 1075 and 3038 also has a very good herbicidal action on broadleaved plants and were tolerated by Indian corn. Compound no. 211 had an excellent herbicidal action and was tolerated by wheat. 

We claim:
 1. Isoxazole-5-carboxamides of the formula I ##STR83## where X is oxygen,R¹ is: hydrogen; C₁ -C₁₀ -alkyl which is unsubstituted or substituted by C₁ -C₃ -alkoxy, C₁ -C₃ -haloalkoxy, halogen, cyano or phenyl, which in turn may be substituted by halogen, C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -haloalkylthio, cyano, or nitro; C₁ -C₄ -alkoxy; C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₄ -alkyl or halogen; phenyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro or cyano; a 5- or 6-membered heterocyclic radical which is unsubstituted or substituted by C₁ -C₄ -alkyl, carboxyl or C₁ -C₄ -alkoxycarbonyl, said heterocyclic radical being attached via carbon and selected from the group consisting of tetrahydrofuryl, tetrahydropyranyl, pyridyl, thienyl, furyl and pyrazolyl;R² is: formyl; 4,5-dihydrooxazol-2-yl; or a radical of the formula --COYR⁵ or --CONR⁶ R⁷, where Y is oxygen or sulfur; R⁵ is: hydrogen; C₁ -C₈ -alkyl which is unsubstituted or substituted by C₁ -C₄ -alkoxy, C₁ -C₄ -alkoxy-C₁ -C₄ -alkoxy, halogen, cyano, hydroxy, trimethylsilyl, C₁ -C₄ -alkylthio, C₁ -C₄ -alkylamino, C₁ -C₄ -dialkylamino, C₁ -C₄ -alkylsulfinyl, C₁ -C₄ -alkylsulfonyl, carboxyl, C₁ -C₄ -alkoxycarbonyl, C₁ -C₄ -dialkyloaminocarbonyl, C₁ -C₄ -dialkoxyphosphonyl, 2-propane-iminooxy, thienyl, furyl, tetrahydrofuryl, phthalimido, pyridyl, benzyloxy, benzoyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₃ -alkoxy or halogen; and phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano; C₃ -C₈ -alkenyl which is unsubstituted or substituted by phenyl which in turn may be substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano; C₃ -C₆ -haloalkenyl; C₃ -C₈ -alkynyl which is unsubstituted or substituted by hydroxy or C₁ -C₄ -alkoxy; C₃ -C₆ -cycloalkyl; C₅ -C₆ -cycloalkenyl; phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro, cyano, C₁ -C₄ -alkoxycarbonyl or formylamino; a 5- or 6-membered heterocyclic radical selected from the group consisting of thienyl, furyl, tetrahydrofuryl, triazolyl bonded via nitrogen, imidazolyl bonded via nitrogen, tetrahydroipyranyl, pyridyl, morpholino bonded via nitrogen, or piperidino bonded via nitrogen; C₆ -C₇ -cycloalkanimino; phthalimido; succinimido; or a radical ##STR84## or one equivalent of a cation from the group consisting of the alkali metals, alkaline earth metals, manganese, copper, iron, ammonium and substituted ammonium; or a radical ##STR85## where R⁸ and R⁹ independently of one another are C₁ -C₄ -alkyl; C₂ -C₆ -alkoxyalkyl; C₃ -C₆ -cycloalkyl; phenyl; furyl; or together form a methylene chain of the formula --(CH₂)_(m) --, where m is from 4 to 7; R⁹ is additionally hydrogen; R⁶ is: hydrogen; C₁ -C₈ -alkyl or C₃ -C₈ -cycloalkyl R⁷ is: hydrogen or C₁ -C₈ -alkyl, or R⁶ and R⁷ form a methylene chain having 4 or 5 members; R³ is: hydrogen; C₁ -C₈ -alkyl which is unsubstituted or substituted by hydroxy, halogen, C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio or C₁ -C₄ -dialkylamino; C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, halogen or C₁ -C₄ -haloalkyl; R⁴ is: hydrogen; hydroxyl; C₁ -C₄ -alkoxy; C₁ -C₁₀ -alkyl which is unsubstituted or substituted by C₁ -C₄ -alkyloxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -dialkylamino, halogen, C₃ -C₆ -cycloalkyl or phenyl, which in turn may be substituted by halogen, cyano, nitro, C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio or C₁ -C₄ -haloalkylthio; C₃ -C₁₀ -alkenyl or C₃ -C₁₀ -alkynyl which is unsubstituted or substituted by halogen or C₁ -C₄ -alkoxy; C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro or cyano; C₁ -C₄ -dialkylamino; a 3-membered to 6-membered heterocyclic radical which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl or halogen, said heterocyclic radical being one member selected from the group consisting of tetrahydropyranyl, tetrahydrofuryl, thiazolyl, pyridyl, pyrimidyl, morpholino bonded via nitrogen and piperidino bonded via nitrogen; phenyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro, cyano, formyl, C₁ -C₆ -alkanoyl or C₁ -C₆ -haloalkanoyl; with the proviso that R¹ is not CH₃ when R² is COOH, COOC₂ H₅ or CONH₂ and R³ and R⁴ are both hydrogen; further proviso that R¹ is not phenyl when R² is COOCH₃ and R³ and R⁴ are both hydrogen; and their agriculturally acceptable salts.
 2. Isoxazole-5-carboxamides of the formula I as set forth in claim 1, where R³ is hydrogen.
 3. Isoxazole-5-carboxamides of the formula I as set forth in claim 1, whereR¹ is: hydrogen or C₁ -C₄ -alkyl; R² is: COYR⁵, where Y is oxygen or sulfur and R⁵ is hydrogen; C₁ -C₄ -alkyl; phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio or halogen; or the radical ##STR86## R³ is hydrogen and R⁴ is C₁ -C₄ -alkyl or C₃ -C₈ -cycloalkyl.
 4. An isoxazole-5-carboxamide of the formula I as set forth in claim 1, where R¹ is n-propyl, R² is propan-2-iminoxycarbonyl, R³ is hydrogen and R⁴ is tert-butyl.
 5. A herbicidal agent comprising an agriculturally acceptable carrier and an isoxazole-5-carboxamide of the formula I as set forth in claim
 1. 6. A process for combating the growth of unwanted plants wherein said plants and/or the area to be kept free of said plants are treated with a herbicidally effective amount of an isoxazole-5-carboxamide of the formula I where ##STR87## X is oxygen, R¹ is hydrogen;C₁ -C₁₀ -alkyl which is unsubstituted or substituted by C₁ -C₃ -alkoxy, C₁ -C₃ -haloalkoxy, halogen, cyano or phenyl, which in turn may be substituted by halogen, C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -haloalkylthio, cyano, or nitro; C₁ -C₄ -alkoxy; C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₄ -alkyl or halogen; phenyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro or cyano; a 5- or 6-membered heterocyclic radical which is unsubstituted or substituted by C₁ -C₄ -alkyl, carboxyl or C₁ -C₄ -alkoxycarbonyl, said heterocyclic radical being attached via carbon and selected from the group consisting of tetrahydrofuryl, tetrahydropyranyl, pyridyl, thienyl, furyl and pyrazolyl; R² is: formyl; 4,5-dihydrooxazol-2-yl; or a radical of the formula --COYR⁵ or --CONR⁶ R⁷, where Y is oxygen or sulfur; R⁵ is: hydrogen; C₁ -C₈ -alkyl which is unsubstituted or substituted by C₁ -C₄ -alkoxy, C₁ -C₄ -alkoxy-C₁ -C₄ -alkoxy, halogen, cyano, hydroxy, trimethylsilyl, C₁ -C₄ -alkylthio, C₁ -C₄ -alkylamino, C₁ -C₄ -dialkylamino, C₁ -C₄ -alkylsulfinyl, C₁ -C₄ -alkylsulfonyl, carboxyl, C₁ -C₄ -alkoxycarbonyl, C₁ -C₄ -dialkyloaminocarbonyl, C₁ -C₄ -dialkoxyphosphonyl, 2-propane-iminooxy, thienyl, furyl, tetrahydrofuryl, phthalimido, pyridyl, benzyloxy, benzoyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₃ -alkoxy or halogen; and phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano; C₃ -C₈ -alkenyl which is unsubstituted or substituted by phenyl which in turn may be substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro or cyano; C₃ -C₆ -haloalkenyl; C₃ -C₈ -alkynyl which is unsubstituted or substituted by hydroxy or C₁ -C₄ -alkoxy; C₃ -C₆ -cycloalkyl; C₅ -C₆ -cycloalkenyl; phenyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl, halogen, nitro, cyano, C₁ -C₄ -alkoxycarbonyl or formylamino; a 5- or 6-membered heterocyclic radical selected from the group consisting of thienyl, furyl, tetrahydrofuryl, triazolyl bonded via nitrogen, imidazolyl bonded via nitrogen, tetrahydropyranyl, pyridyl, morpholino bonded via nitrogen, or piperidino bonded via nitrogen; C₆ -C₇ -cycloalkanimino; phthalimido; succinimido; or a radical ##STR88## or one equivalent of a cation from the group consisting of the alkali metals, alkaline earth metals, manganese, copper, iron, ammonium and substituted ammonium; or a radical ##STR89## where R⁸ and R⁹ independently of one another are C₁ -C₄ -alkyl; C₂ -C₆ -alkoxyalkyl; C₃ -C₆ -cycloalkyl; phenyl; furyl; or together form a methylene chain of the formula --(CH₂)_(m) --, where m is from 4 to 7; R⁹ is additionally hydrogen; R⁶ is: hydrogen; C₁ -C₈ -alkyl or C₃ -C₈ -cycloalkyl R⁷ is: hydrogen or C₁ -C₈ -alkyl, or R⁶ and R⁷ form a methylene chain having 4 or 5 members; R³ is: hydrogen; C₁ -C₈ -alkyl which is unsubstituted or substituted by hydroxy, halogen, C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio or C₁ -C₄ -dialkylamino; C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₄ -alkyl, halogen or C₁ -C₄ -haloalkyl; R⁴ is: hydrogen; hydroxyl; C₁ -C₄ -alkoxy; C₁ -C₁₀ -alkyl which is unsubstituted or substituted by C₁ -C₄ -alkyloxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -dialkylamino, halogen, C₃ -C₆ -cycloalkyl or phenyl, which in turn may be substituted by halogen, cyano, nitro, C₁ -C₄ -alkyl, C₁ -C₄ -haloalkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkoxy, C₁ -C₄ -alkylthio or C₁ -C₄ -haloalkylthio; C₃ -C₁₀ -alkenyl or C₃ -C₁₀ -alkynyl which is unsubstituted or substituted by halogen or C₁ -C₄ -alkoxy; C₃ -C₈ -cycloalkyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro or cyano; C₁ -C₄ -dialkylamino; a 3-membered to 6-membered heterocyclic radical which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl or halogen, said heterocyclic radical being one member selected from the group consisting of tetrahydropyranyl, tetrahydrofuryl, thiazolyl, pyridyl, pyrimidyl, morpholino bonded via nitrogen and piperidino bonded via nitrogen; phenyl which is unsubstituted or substituted by C₁ -C₆ -alkyl, C₁ -C₆ -haloalkyl, C₁ -C₆ -alkoxy, C₁ -C₆ -haloalkoxy, C₁ -C₆ -alkylthio, C₁ -C₆ -haloalkylthio, halogen, nitro, cyano, formyl, C₁ -C₆ -alkanoyl or C₁ -C₆ -haloalkanoyl; and their agriculturally acceptable salts. 